Plants both lose water and take in carbon dioxide through microscopic stomatal pores, each of which is regulated by a surrounding pair of guard cells. During drought, the plant hormone abscisic acid (ABA) inhibits stomatal opening and promotes stomatal closure, thereby promoting water conservation. Dozens of cellular components have been identified to function in ABA regulation of guard cell volume and thus of stomatal aperture, but a dynamic description is still not available for this complex process. Here we synthesize experimental results into a consistent guard cell signal transduction network for ABA-induced stomatal closure, and develop a dynamic model of this process. Our model captures the regulation of more than 40 identified network components, and accords well with previous experimental results at both the pathway and whole-cell physiological level. By simulating gene disruptions and pharmacological interventions we find that the network is robust against a significant fraction of possible perturbations. Our analysis reveals the novel predictions that the disruption of membrane depolarizability, anion efflux, actin cytoskeleton reorganization, cytosolic pH increase, the phosphatidic acid pathway, or K(+) efflux through slowly activating K(+) channels at the plasma membrane lead to the strongest reduction in ABA responsiveness. Initial experimental analysis assessing ABA-induced stomatal closure in the presence of cytosolic pH clamp imposed by the weak acid butyrate is consistent with model prediction. Simulations of stomatal response as derived from our model provide an efficient tool for the identification of candidate manipulations that have the best chance of conferring increased drought stress tolerance and for the prioritization of future wet bench analyses. Our method can be readily applied to other biological signaling networks to identify key regulatory components in systems where quantitative information is limited. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2013-06-20T03:09:04Z 2017-07-19T12:01:07Z

\r\n \r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Abscisic Acid</font></p><p><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">15</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">20</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">4</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 264.3169</span></font></p><p><font face="Georgia" size="2">PubChem ID: <span style="line-height: 19px; background-color: rgb(255, 255, 255);"> </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=5280896[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">5280896</a> </font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:06:14Z

<span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Nuclear cap-binding protein subunit 1</font></span><div><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Part of a cap binding complex that binds the 5' mRNA cap. </font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9SIU2" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9SIU2</a></font></div><div><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: ABH1</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">815840</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">G-protein-coupled receptor 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (thale cress)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O04714" style="text-decoration: none; background-color: rgb(255, 255, 255);">O04714</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/841247" ref="ordinalpos=2&ncbi_uid=841247&link_uid=841247" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">GCR1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">841247</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Farnesyltransferase subunit beta [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (thale cress)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q38920" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q38920</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/834026" ref="ordinalpos=1&ncbi_uid=834026&link_uid=834026" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">ERA1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">834026</span></font></div>

2015-11-15T18:06:14Z

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Represents Ca<span style="vertical-align: 4pt;">2+</span><span style="vertical-align: 4pt;"> </span>influx across the plasma membrane [1]. </font></p></div></div>\r\n </div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">K<sup>+</sup> efflux through slowly activating outwardly-rectifying K<sup>+</sup><span style="vertical-align: 4pt;"> </span>channels at the plasma membrane [1]. </font>

2017-07-19T12:01:07Z

<font face="Georgia" size="2">Nitric Oxide</font><div><font face="Georgia" size="2">PubChem ID: <a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=145068[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">145068</a><br/></font><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> NO   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 30.0061 </span></font></div></div>

2015-11-15T18:06:14Z

<font size="2" face="Georgia">Phosphoenolpyruvate carboxylase</font><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9MAH0" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9MAH0</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/841765" ref="ordinalpos=2&ncbi_uid=841765&link_uid=841765" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PPC1</a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">841765</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">K<sup>+</sup> efflux from the vacuole to the cytosol  [1]. </font>

2017-07-19T12:01:07Z

<font face="Georgia" size="2">Sphingosine Kinase </font><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9NYA1" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9NYA1</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/8877" ref="ordinalpos=1&ncbi_uid=8877&link_uid=8877" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">SPHK1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: 8877</font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Protein Kinase Open Stomata 1</font><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q940H6" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q940H6</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/829541" ref="ordinalpos=1&ncbi_uid=829541&link_uid=829541" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">OST1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">829541</span></font></div><div><font face="AdvPSMy"><span style="font-size: 11px;"><br/></span></font></div>

2015-11-15T18:06:14Z

<div style="font-style: normal;"><font face="Georgia" size="2"><br/></font></div><div><font face="Georgia" size="2">Actin (<em>Homo sapiens</em>)</font></div><font face="Georgia" size="2">Uniprot ID: <a href="http://www.uniprot.org/uniprot/P60709" style="font-style: normal; text-decoration: none; background-color: rgb(255, 255, 255);">P60709</a></font><div><font face="Georgia" size="2">Gene Name: ACTB </font></div><div><font face="Georgia" size="2">Gene ID: 60<br/></font><div style="font-style: normal;"><font face="Georgia" size="2"><br/></font></div><div style="font-style: normal;"><font face="Georgia" size="2">In "Guard Cell Abscisic Acid Signaling", this node represents actin cytoskeleton reorganization of plant guard cells [1]. </font></div><div style="font-style: normal;"><font face="Georgia" size="2">Actin (<em class="tax" style="line-height: 1.5;">Arabidopsis thaliana)</em></font></div><div style="font-style: normal;"><font face="Georgia" size="2"> UniProt ID: <a href="http://www.uniprot.org/uniprot/P53497" style="text-decoration: none; background-color: rgb(255, 255, 255);">P53497</a></font></div><div style="font-style: normal;"><font face="Georgia" size="2">Gene Name: ACT12</font></div><div style="font-style: normal;"><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">823805</span></font></div></div>

2017-05-18T11:57:21Z

<span style="background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">H(+)-ATPase 1 [</span><em style="line-height: 18.88888931274414px;">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px;"> (thale cress)]</span></font></span><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P20649" style="text-decoration: none;">P20649</a></font></span></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene Name:</span><a href="http://www.ncbi.nlm.nih.gov/gene/816413" ref="ordinalpos=17&ncbi_uid=816413&link_uid=816413" style="line-height: 18.88888931274414px; white-space: nowrap;">HA1</a></font></span></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene ID: </span><span style="line-height: 17.77777862548828px;">816413</span></font></span></div>

2017-07-19T12:01:07Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Guanine nucleotide-binding protein alpha-1 subunit [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(thale cress)]</span><br/></font><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P18064" style="text-decoration: none; background-color: rgb(255, 255, 255);">P18064</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/817170" ref="ordinalpos=14&ncbi_uid=817170&link_uid=817170" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">GP ALPHA 1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">817170</span></font></div>

2015-11-15T18:06:14Z

Uniprot ID: <a href="http://www.uniprot.org/uniprot/Q13393">Q13393</a><br/><div><span style="font-size: 10pt;">Uniprot ID: </span><a href="http://www.uniprot.org/uniprot/O14939" style="font-size: 10pt;">O14939</a></div><div><span style="font-size: 10pt;">Uniprot ID: </span><a href="http://www.uniprot.org/uniprot/Q8N7P1" style="font-size: 10pt;">Q8N7P1</a></div><div><span style="font-size: 10pt;">Uniprot ID: </span><a href="http://www.uniprot.org/uniprot/Q8IV08" style="font-size: 10pt;">Q8IV08</a></div><div><span style="font-size: 10pt;">Uniprot ID: </span><a href="http://www.uniprot.org/uniprot/Q8N2A8" style="font-size: 10pt;">Q8N2A8</a></div><div><span style="font-size: 10pt;">Uniprot ID:</span> <a href="http://www.uniprot.org/uniprot/Q96BZ4" style="font-size: 10pt;">Q96BZ4</a></div>

2015-11-15T18:06:14Z

<span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Inositol hexaphosphate</font></span><div><font face="Georgia" size="2"><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">PubChem ID: </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=890[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; color: rgb(0, 86, 204); background-color: rgb(255, 255, 255);">890</a></font></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">6</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">18</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">24</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">P</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">6</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);"> 660.035292</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Represents anion efflux at the plasma membrane [1]. </font>

2017-07-19T12:01:07Z

<font face="Georgia" size="2">Represents CA<sup>2+</sup> increase in the cytosol [1]. </font>

2017-07-19T12:01:07Z

<font face="Arial, Verdana" size="2">Represents reactive oxygen intermediaries/species.</font>

2015-11-15T18:06:14Z

<div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Represents two protein phosphatases [1]:</font></span></div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"></span></font><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font size="2" face="Georgia"><br/></font></span></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font size="2" face="Georgia">Protein Phosphatase 2C 56</font></span></div><font size="2" face="Georgia">UniProt ID: <a href="http://www.uniprot.org/uniprot/P49597" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49597</a></font><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: ABI1</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">NCBI Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 18.877840042114258px;">828714</span></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><br/></font></span></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Protein Phosphatase 2C 77</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O04719" style="text-decoration: none; background-color: rgb(255, 255, 255);">O04719</a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: ABI2</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">NCBI Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">835809</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Plasma membrane depolarization [1]. </font>

2017-07-19T12:01:07Z

<font face="Georgia" size="2">Represents Ca<sup>2+ </sup>and Ca<sup>2+</sup>/H<sup>+</sup> antiporters responsible for Ca<sup>2+ </sup>efflux at the plasma membrane [1]. </font><div><font face="Georgia" size="2">Includes: </font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 1</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q37145" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q37145</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA1</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">839670</span></font></div><div><div><font face="Georgia" size="2">Calcium-transporting ATPase 2</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/O81108" style="text-decoration: none; background-color: rgb(255, 255, 255);">O81108</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA2</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">829918</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 3</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P92939" style="text-decoration: none; background-color: rgb(255, 255, 255);">P92939</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA3</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">830296</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 4</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/O23087" style="text-decoration: none; background-color: rgb(255, 255, 255);">O23087</a></font></div><div><font face="Georgia" size="2">Gene Name: ECA4</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">837280</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 5</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/O23087" style="text-decoration: none; background-color: rgb(255, 255, 255);">O23087</a></font></div><div><font face="Georgia" size="2">Gene Name: <span style="background-color: rgb(255, 255, 255); line-height: 19.49652862548828px;">ECA2</span></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">827984</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 6</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9SY55" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9SY55</a></font></div><div><font face="Georgia" size="2">Gene Name: <span style="background-color: rgb(255, 255, 255); line-height: 19.49652862548828px;">ECA3</span></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">837550</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 7</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/O64806" style="text-decoration: none; background-color: rgb(255, 255, 255);">O64806</a></font></div><div><font face="Georgia" size="2">Gene Name: At2g22950</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">816826</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 8</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9LF79" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9LF79</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA8</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">835815</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 9</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9LU41" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9LU41</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA9</font></div><div><font face="Georgia" size="2">Gene ID: <span style="line-height: 16.78819465637207px; background-color: rgb(255, 255, 255);"> </span></font><dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap; line-height: 16.78819465637207px; background-color: rgb(255, 255, 255);">821671</dd></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 10</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9SZR1" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9SZR1</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA10</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">829112</span></font></div><div><font face="Georgia" size="2">Calcium-transporting ATPase 11</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9M2L4" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9M2L4</a></font></div><div><font face="Georgia" size="2">Gene Name: ACA11</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">824900</span></font></div></div><div><font face="Georgia" size="2"><br/></font></div><div><font face="Georgia" size="2">and calcium/proton anitporters, such as: </font></div><div><font face="Georgia" size="2">Cation Exchanger 6</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9LFZ8" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9LFZ8</a></font></div><div><font face="Georgia" size="2">Gene Name: CAX6</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">842021</span></font></div>

2015-11-15T18:06:14Z

<span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Inositol polyphosphate multikinase alpha</font></span><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9LY23" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9LY23</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene Name: </span><span style="background-color: rgb(255, 255, 255); line-height: 19.49652862548828px;">IPK2a</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">830628</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Represents closure of stomatal pores [1]. </font>

2015-11-15T18:06:14Z

Represents pH<div><br/></div><div>Phagocytosis (mouse) in coninfection for more info:</div><div>http://www.ncbi.nlm.nih.gov/mesh/68010587</div><div><hr/></div><div><br/></div><div>PH protein in the Drosophila segmentation model (2013)</div>

2015-11-15T18:06:14Z

<div><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Malate</font></span></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">PubChem ID: </span><span style="color: rgb(85, 85, 85); line-height: 19px; background-color: rgb(255, 255, 255);"> </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=525[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; color: rgb(0, 86, 204); background-color: rgb(255, 255, 255);">525</a><span style="color: rgb(85, 85, 85); line-height: 19px; background-color: rgb(255, 255, 255);"><br/></span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">4</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">6</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">5</sub><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; color: rgb(85, 85, 85); background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="color: rgb(85, 85, 85); line-height: 17px; background-color: rgb(255, 255, 255);"> 134.08744 </span></font></div>

2015-11-15T18:06:14Z

<div><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);"><span style="line-height: 19px;"><font face="Georgia" size="2">Cyclic GMP</font></span></span></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);"><span style="line-height: 19px;">PubChem ID:</span></span><span style="line-height: 19px;"> </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=24316[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px;">24316</a></font></div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">10</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">12</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">N</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">5</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">7</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 345.205342</span></font>

2015-11-15T18:06:14Z

<span style="line-height: 17px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Inositol 1,4,5-triphosphate</font></span><div><font face="Georgia" size="2"><span style="line-height: 17px; background-color: rgb(255, 255, 255);">PubChem ID: </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=55310[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">55310</a></font></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">6</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">15</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">15</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">3</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 420.095586</span></font></div><div><span style="line-height: 17px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><br/></font></span></div><div style="font-size: 10pt; font-family: Arial, Verdana; font-weight: normal;"><span style="color: rgb(85, 85, 85); font-family: Arial, Verdana, sans-serif; line-height: 17px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Guanosine cyclase </font><div><font size="2" face="Georgia">May be membrane bound, or soluble to the cytosol. Many channel proteins also have guanosine cyclase activity in plants. <br/></font><div><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">In humans, soluble GC is a heterodimeric protein composed of one alpha subunit and one beta subunit. </font></span></div><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Guanylate cyclase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> 1, soluble, alpha 3</span><br/></font><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q02108" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q02108</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/2982" ref="ordinalpos=7&ncbi_uid=2982&link_uid=2982" style="color: rgb(100, 42, 143); line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">GUCY1A3</a></font></div><div><font face="Georgia" size="2">Gene ID: 2982</font></div></div></div><div><font face="Georgia" size="2"><br/></font></div><div style="font-family: Arial, Verdana; font-size: 10pt;"><font face="Georgia" size="2"><br/></font></div>

2015-11-15T18:06:14Z

<div><span style="border: 0px; outline: 0px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255); line-height: 17px;"><font size="2" face="Georgia">Phosphatidic acid</font></span></div><div style="font-style: normal; font-variant: normal; line-height: normal;"><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">PubChem ID: </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=5460104[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">5460104</a><span style="line-height: 19px; background-color: rgb(255, 255, 255);"><br/></span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">5</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">9</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">8</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 228.093922</span></font></div>

2015-11-15T18:06:14Z

<div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Ras-related C3 botulinum toxin substrate 1 </font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(rho family, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">small</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> GTP binding protein </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Rac1</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P63000" style="text-decoration: none; background-color: rgb(255, 255, 255);">P63000</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5879" ref="ordinalpos=1&ncbi_uid=5879&link_uid=5879" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">RAC1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: 5879</font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Represents nitrate reductase [1], either: </font><div><font face="Georgia" size="2">Nitrate Reductase 1 (<em>Arabidopsis thaliana</em>)</font></div><div style="font-style: normal;"><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P11832" style="text-decoration: none; background-color: rgb(255, 255, 255);">P11832</a></font></div><div style="font-style: normal;"><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/844112" ref="ordinalpos=1&ncbi_uid=844112&link_uid=844112" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">NIA1</span></a></font></div><div style="font-style: normal;"><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">844112</span></font></div><div style="font-style: normal;"><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">Nitrate Reductase 2 </span>(<em>Arabidopsis thaliana</em>)</font></div><div style="font-style: normal;"><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P11035" style="text-decoration: none; background-color: rgb(255, 255, 255);">P11035</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/840630" ref="ordinalpos=1&ncbi_uid=840630&link_uid=840630" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">NIA2</span></a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">840630</span></font></div></div><div style="font-size: 10pt; font-family: Arial, Verdana; font-style: normal;"><br/></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Serine/threonine-protein phosphatase 2A regulatory subunit A alpha isoform [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (thale cress)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q38845" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q38845</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/839135" ref="ordinalpos=2&ncbi_uid=839135&link_uid=839135" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">RCN1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">839135</span></font></div>

2015-11-15T18:06:14Z

<span style="font-style: normal;">ADP Ribose Cyclase (</span><em>Homo sapiens</em>)<div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P28907" style="text-decoration: none; font-family: sans-serif; font-size: small; background-color: rgb(255, 255, 255);">P28907</a></div><div>Gene Name: CD38</div><div>Gene ID: <span style="background-color: rgb(255, 255, 255); font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 18.88888931274414px;">952</span></div><div><br/><div style="font-style: normal;"><br/></div></div>

2015-11-15T18:06:14Z

<div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Rac-like GTP-binding protein ARAC8 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(thale cress)]</span></font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9SU67" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9SU67</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/823959" ref="ordinalpos=1&ncbi_uid=823959&link_uid=823959" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">ROP10</span></a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">823959</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">Cyclic ADP-ribose</font><div><font face="Georgia" size="2">PubChem ID: <a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=123847[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">123847</a></font></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">15</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">21</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">N</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">5</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">13</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">2</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 541.300464</span></font></div><div><span style="line-height: 19px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">A pyridine nucleotide that mobilizes CALCIUM.</font></span></div>

2015-11-15T18:06:14Z 2015-11-15T18:06:14Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Rac-like GTP-binding protein ARAC4 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (thale cress)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q38919" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q38919</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name:</span><a href="http://www.ncbi.nlm.nih.gov/gene/838598" ref="ordinalpos=2&ncbi_uid=838598&link_uid=838598" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">ROP2</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">838598</span></font></div>

2015-11-15T18:06:14Z

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">K<sup>+</sup><span style="vertical-align: 4pt;"> </span>efflux through rapidly activating K<sup>+</sup><span style="vertical-align: 4pt;"> </span>channels (AP channels) at the plasma membrane. </font><span style="font-size: small; font-family: Georgia;">The K</span><span style="font-size: small; font-family: Georgia; vertical-align: 6pt;">+ </span><span style="font-size: small; font-family: Georgia;">AP current is a transient K</span><span style="font-size: small; font-family: Georgia; vertical-align: 6pt;">+ </span><span style="font-size: small; font-family: Georgia;">current which was observed in Arabidopsis guard cells only [1,2]. </span></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:06:14Z

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Ca<sup>2+</sup> influx to the cytosol from intracellular stores [1].  </font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:06:14Z

<div>\r\n \r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Heterotrimeric G protein b component </font></p><p><span style="line-height: 21.111112594604492px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Also known as: Guanine nucleotide-binding protein subunit beta</font></span></p><p><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P49177" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49177</a></font></p></div></div></div></div><div><font face="Georgia" size="2">Gene Name: AGB1</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">829597</span></font></div>

2015-11-15T18:06:14Z

<font face="Georgia" size="2">NADPH oxidase</font><div><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">respiratory burst oxidase</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O48538" style="text-decoration: none; background-color: rgb(255, 255, 255);">O48538</a></font></div><div><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: RBOH F</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.49652862548828px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">842710</span></font></div>

2015-11-15T18:06:14Z

<div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Phosphoinositide phospholipase C 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Arabidopsis thaliana</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (thale cress)]</span></font></div><font face="Georgia" size="2">Uniprot ID: <a href="http://www.uniprot.org/uniprot/Q39032" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q39032</a></font><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/835981" ref="ordinalpos=2&ncbi_uid=835981&link_uid=835981" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">PLC1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">835981</span></font></div>

2015-11-15T18:06:14Z

<div><font face="Georgia" size="2">Sphingosine-1-phosphate</font></div><div><font face="Georgia" size="2">PubChem ID: <a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=5283560[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">5283560</a></font></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">18</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">38</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">NO</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">5</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 379.471782</span></font></div>

2015-11-15T18:06:14Z

\r\n \r\n \r\n <div class="page" title="Page 3">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">CaIM is activated by ROS or the absence of ERA1 or the absence of ABH1. Depolarization is a negative regulator and is dominant over all regulators [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">CaIM was hypersensitive to ABA in the </span><span style="font-family: Georgia; font-size: small; font-style: italic;">era1 </span><span style="font-family: Georgia; font-size: small;">mutant, but the hyperpolarization-induced activation threshold of CaIM showed little change [1,6]. </span>

<font face="Georgia">ABH1 promotes CaIM [1,2,3]. </font><span style="font-family: Georgia; font-size: small;">The </span><span style="font-family: Georgia; font-size: small; font-style: italic;">abh1 </span><span style="font-family: Georgia; font-size: small;">mutant has a similar phenotype to </span><span style="font-family: Georgia; font-size: small; font-style: italic;">era1</span><span style="font-family: Georgia; font-size: small;">, except only hypersensitivity in ABA induced Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+</span><span style="font-family: Georgia; font-size: small; vertical-align: -1pt;">c </span><span style="font-family: Georgia; font-size: small;">was reported. Here we hypothesize that ABH1 is regulating CaIM; we evaluated the possibility of ABH1 regulating CIS instead, and the results were similar [1]. </span>

<span style="font-family: Georgia; font-size: small;">Calcium influx across the plasma membrane requires hyperpolarization [1,5]. </span><font face="Georgia" size="2">Depolarization inhibits calcium influx at the membrane [1,4].</font>

<span style="font-family: Georgia; font-size: small;">Calcium influx across the plasma membrane requires both hyperpolarization and ROS production [1,5]</span>

S_15 1 S_17 1 S_41 1 S_30 1 S_17 1 S_30 1 S_41 1 S_17 1 S_41 1 S_30 1 S_17 1 S_15 1

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">KOUT has two activators: pH and depolarization. pH requires depolarization to activate KOUT. ROS and NO are inhibitors of KOUT but are overcome if both KOUT and pH are active [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">The activity of outwardly rectifying K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">currents is activated by cytosolic pH increase [1,2].</span>

<span style="font-family: Georgia; font-size: small;">KOUT is inhibited by ROS [1,3].</span>

<span style="font-family: Georgia; font-size: small;">Membrane depolarization will drive K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">flow out of the cell [1,2]. </span>

<span style="font-family: Georgia; font-size: small;">KOUT is inhibited by nitric oxide [1,4]. </span>

S_21 1 S_17 1 S_17 1 S_15 1 S_3 1

<font face="Georgia" size="2">NO and NIA are both required for activation of NO [1]. </font>

<span style="font-family: Georgia; font-size: small;">NOS  mediates NO production [1,3]. </span>

\r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">NIA mediates NO\r\nproduction [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_35 1 S_28 1

<span style="font-family: Georgia; font-size: small;">ABA inhibits PEPC [1]. </span>

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ABA inhibits PEPC activity in guard cells [1,2].  </font></p>\r\n </div>\r\n </div>\r\n </div>

S_29 1

<font face="Georgia" size="2">Ca<sup>2+</sup> activates KEV [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Calcium-induced K release through K -permeable channels in the tonoplast [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_14 1

<span style="font-family: Georgia; font-size: small;">ABA activates SphK [1,2]. </span>

\r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ABA activates SphK [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_29 1

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">ABA activates OST1 [1]. </span>

<font face="Georgia" size="2">ABA activates OST1 [1,2]. </font>

S_29 1

<font face="Georgia" size="2">Ca<sup>2+</sup><sub>c</sub> promotes actin reorganization, while RAC1 inhibits actin reorganization and is dominant over the activity of Ca<sup>2+</sup><sub>c </sub>[1]. </font>

<font face="Georgia" size="2">Ca<sup>2+</sup> flux promotes actin reorganization [1,3]. </font>

<font face="Georgia" size="2">RAC inhibits actin reorganization [1,2]. </font>

S_14 1 S_14 1 S_27 1

<font face="Georgia" size="2">Ca<sup>2+</sup>, pH and ROS each inhibit HTPase [1]. </font>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">pH inhibits HTPase [1,3]. </span>

<font face="Georgia" size="2">Ca<sup>2+ </sup>influx inhibits HTPase [1,2]. </font>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">ROS inhibits HTPase [1,4]. </span>

S_15 1 S_14 1 S_21 1

<font face="Georgia" size="2">GPA1 can be activated by the presence of AGB1, or AGB1 and S1P in the presence of GCR1. GCR1 is a negative regulator of GPA1 and is dominant over AGB1 when it is the only positive regulator present [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">GCR1 is a negative regulator of the ABA and S1P signal in\r\nguard cells and it can interact with GPA1 [2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">AGB1 is the sole\r\nArabidopsis G? subunit and activates GPA1 [1,3]. </font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">S1P\r\nactivates PLD through GPA1[1].  </font></p>\r\n </div>\r\n </div>\r\n </div>

S_39 1 S_40 1 S_44 1 S_39 1

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">GPA1 activates PLD [1]. </span>

<font face="Georgia" size="2">GPA1 activates PLD [1,2]. </font>

S_10 1

<font face="Georgia" size="2">InsPK activates InsP6 [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">InsPK represents the known last steps in  InsP6 production [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_19 1

<font face="Georgia" size="2">Ca<sup>2+</sup><sub>c</sub> and pH activates anionEM, while ABI1 inhibits anionEM.  If ABI1 is present, both positive regulators (cytosolic Ca<span style="vertical-align: 6pt;">2+ </span>and cytosolic pH) are required to activate the anion efflux; if ABI1 is not present, only one positive regulator is required to activate the anion efflux</font><font face="Georgia" size="2"> [1]. <br/></font><div style="font-size: 10pt; font-family: Arial, Verdana;"><div class="page" title="Page 3"><div class="layoutArea"><div class="column">\r\n </div>\r\n </div>\r\n </div></div>

<span style="font-family: Georgia; font-size: small;">ABI1 is a negative regulator of anion efflux</span><font face="Georgia" size="2"> [1,2,3,5]. </font>

<span style="font-size: small; font-family: Georgia;">Anion efflux through the membrane was shown to be upregulated by pH increase </span><font face="Georgia">[1,2,4,5]. </font><font face="Georgia" size="2"> </font>

<span style="font-family: Georgia; font-size: small;">Anion efflux through the membrane was shown to be upregulated by cytosolic Ca </span><font face="Georgia" size="2">[1,2,4,5]. </font>

S_14 1 S_21 1 S_16 1 S_21 1 S_14 1 S_16 1

\r\n \r\n \r\n <div class="page" title="Page 3">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">CaIM and CIS activate Ca<sup>2+</sup> influx from the cytosol, while Ca<sup>2+ </sup>ATPase inhibits Ca<sup>2+</sup> influx and is dominant over both positive regulators [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">CaIM promotes pathway from ABA to K<sup>+</sup> outflow by producing Ca<sup>2+</sup> [1,3]. </font>

<font face="Georgia" size="2">Ca<sup>2+</sup> ATPase inhibits Ca<sup>2+</sup><sub>c</sub> [1,2]. </font>

<font face="Georgia">CIS activates Ca<sup>2+</sup><sub>c</sub> [1,4]. </font>

S_38 1 S_18 1 S_1 1 S_18 1

<font face="Georgia" size="2">Atrboh activates ROS [1]. </font>

<font face="Georgia" size="2">ROS production is catalyzed by Atrboh [1,2]. </font>

S_42 1

<font face="Georgia" size="2">The activation of ABI1 requires an increase in cytosolic pH. PA and ROS are both negative regulators of ABI1 and are dominant over pH [1]. </font>

<font face="Georgia" size="2">ABI1 has been shown to be upregulated by cytosolic pH [1,3].</font>

<font face="Georgia" size="2">A recent paper shows that ABI1 is relocated from the cytosol to the plasma membrane by binding to phosphatidic acid [2], therefore PA negatively regulates ABI1 activity [1]. </font>

<font face="Georgia" size="2">ABI1 has been shown to be negatively regulated by ROS [1,4].</font>

S_21 1 S_26 1 S_15 1

\r\n \r\n \r\n <div class="page" title="Page 3">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Here, K<span style="vertical-align: 6pt;">+ </span>release from the vacuole to the cytosol\r\nand anion efflux and calcium influx across the plasma membrane are modeled as positive regulators of\r\ndepolarization, and plasma membrane H<span style="vertical-align: 6pt;">+ </span>ATPase and outwardly rectifying K<span style="vertical-align: 6pt;">+ </span>efflux at\r\nthe membrane as negative regulators of the depolarization process [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">The efflux of positive/negative ions out of the cytosol will hyperpolarize/depolarize the cell. Here, K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">release from the vacuole to the cytosol and anion efflux and calcium influx across the plasma membrane are modeled as positive regulators of depolarization [1]. </span>

<font face="Georgia" size="2">The efflux of positive/negative ions out of the cytosol will hyperpolarize/depolarize the cell. Here, K<span style="vertical-align: 6pt;">+ </span>release from the vacuole to the cytosol and anion efflux and calcium influx across the plasma membrane are modeled as positive regulators of depolarization [1]. </font>

<span style="font-family: Georgia; font-size: small;">Plasma membrane H</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">ATPase and outwardly rectifying K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">efflux at the membrane as negative regulators of the depolarization process [1]. </span>

S_14 1 S_5 1 S_9 1 S_13 1 S_5 1 S_14 1 S_2 1 S_2 1 S_13 1 S_5 1 S_14 1 S_9 1 S_13 1 S_13 1 S_5 1 S_14 1 S_2 1 S_9 1

<font face="Georgia" size="2">Ca<sup>2+ </sup>activates Ca<sup>2+</sup> ATPase [1]. </font>

<div class="page" title="Page 3"><div class="layoutArea"><div class="column"><p><font face="Georgia" size="2">Ca<span style="vertical-align: 6pt;">2+ </span>efflux from the cytosolic compartment activates Ca<sup>2+</sup> channels,\r\nincluding Ca<span style="vertical-align: 6pt;">2+ </span>ATPases and Ca<span style="vertical-align: 6pt;">2+</span>/H<span style="vertical-align: 6pt;">+ </span>antiporters, as the node Ca<span style="vertical-align: 6pt;">2+ </span>ATPase [1,2,3,4,5]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_14 1

<font face="Georgia" size="2">ABA activates InsPK [1]. </font>

<font face="Georgia" size="2">ABA induces InsP6 production in guard cells through the InsPK pathway [1,2]. </font>

S_29 1

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" style="font-size: 10pt;">AnionEM and actin can activate stomatal closure in the presence of </font><span style="font-size: small; font-family: Georgia;">K</span><sup style="font-family: Georgia;">+ </sup><span style="font-size: small; font-family: Georgia;">flux in or out of the cell. Malate is a negative regulator of closure and is dominant over all activators [1].</span></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">Stomatal closure requires anion efflux from membrane [1,2,7.8]. </span>

<span style="font-size: small; font-family: Georgia;">Stomatal closure requires potassium efflux via either slow outwardly rectifying K</span><span style="font-size: small; font-family: Georgia; vertical-align: 6pt;">+</span><span style="font-size: small; font-family: Georgia;">channels [1,3] or fast transient (AP) K</span><span style="font-size: small; font-family: Georgia; vertical-align: 6pt;">+ </span><span style="font-size: small; font-family: Georgia;">channels [1,4]. </span>

<span style="font-family: Georgia; font-size: small;">Stomatal closure requires potassium efflux via either slow outwardly rectifying K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+</span><span style="font-family: Georgia; font-size: small;">channels [1,3] or fast transient (AP) K</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">+ </span><span style="font-family: Georgia; font-size: small;">channels [1,4]. </span>

<span style="font-family: Georgia; font-size: small;">Closure requires the reorganization of the actin cytoskeleton [1,6].</span>

<span style="font-family: Georgia; font-size: small;">Malate is a negative regulator of stomatal closure through its effect of osmotic regulation [1,5].</span>

S_37 1 S_8 1 S_13 1 S_22 1 S_2 1 S_13 1 S_8 1 S_22 1

<font face="Georgia" size="2">ABA activates pH [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ABA induces cytosolic pH increase (pH<span style="vertical-align: -1pt;">c</span>) [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_29 1

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Malate is activated by PEPC and inhibited by ABA and AnionEM. Both inhibitors are dominant over PEPC [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">Anion efflux negatively regulates intracellular malate concentration by releasing malate from the cytosol [1,4]. </span>

<span style="font-family: Georgia; font-size: small;">ABA inhibits PEPC activity in guard cells [1,2]. </span><span style="font-family: Georgia; font-size: small;">ABA also regulates malate concentration by inducing malate breakdown [1,3].</span>

<span style="font-family: Georgia; font-size: small;">PEPC is an upstream enzyme of malate biosynthesis [1,3]. </span>

S_4 1 S_13 1 S_29 1

<font face="Georgia" size="2">GC activates cGMP [1]. </font>

<font face="Georgia" size="2">G</font><span style="font-family: Georgia; font-size: small;">uanyl cyclase (GC) catalyzes cGMP formation [1,2]. </span>

S_25 1

<span style="font-family: Georgia; font-size: small;">PLC activates InsP3 [1]. </span>

\r\n \r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">PLC represents the known last steps in the\r\ncatalysis of InsP3 [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_43 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">NO activates GC [1].</span>

\r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">cGMP is downstream of the nitric oxide\r\npathway in regulation of guard cell closure. NO activates GC [1,2,3].</font></p>\r\n </div>\r\n </div>\r\n </div>

S_3 1

<span style="font-family: Georgia; font-size: small;">Phospholipase D activtes phosphatidic acid (PA) [1]. </span>

\r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Phospholipase D catalyzes the\r\nproduction of phosphatidic acid (PA) [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_11 1

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ABA and ABI1 inhibit RAC1 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">ABI1 negatively regulates ABA inhibition of RAC1 [1,2,3]. </span>

<span style="font-family: Georgia; font-size: small;">ABA inhibits RAC1 [1,2,3]. </span>

S_29 1 S_16 1

<font face="Georgia" size="2">NIA12 is activated by RCN1 [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Nitric reductase\r\n(NIA12) activity is regulated by PP2A(RCN1) based on the well conserved NIA12\r\nregulation mechanism [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_31 1

<span style="font-family: Georgia; font-size: small;">RCN1 activates ABA [1]. </span>

<font face="Georgia" size="2">RCN1 activates ABA [1,2]. </font>

S_29 1

<font face="Georgia">NO activates of ADPRc [1]. </font>

<font face="Georgia" size="2">NO promotes ACPRc activity [1,2]. </font>

S_3 1

<span style="font-family: Georgia; font-size: small;">ERA1 promotes ROP10 [1]. </span>

<font face="Georgia" size="2">ERA1 promotes ROP10 [1,2]. </font>

S_41 1

<font face="Georgia" size="2">ADPRc activates cADPR [1]. </font>

\r\n \r\n \r\n \r\n <font face="Georgia" size="2">ADP ribose cyclase (ADPRc) catalyzes cADPR formation [1,2]. </font>

S_32 1

S_14 1

<span style="font-family: Georgia; font-size: small;">PA promotes ROP2 [1]. </span>

<font face="Georgia" size="2">PA promotes ROP2 [1,2]. </font>

S_26 1

\r\n \r\n \r\n <div class="page" title="Page 4">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">KAP is activated by depolarization but inhibited by Ca<sup>2+</sup> and pH [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">KAP is inhibited by both pH and cytosolic calcium [1,2]. </span>

<span style="font-family: Georgia; font-size: small;">The activation of KAP also requires depolarization of the membrane potential [1,2]. </span>

S_17 1 S_14 1 S_21 1

<font face="Georgia" size="2">The presence of both cADPR and cGMP can activate CIS, or the presence of both InsP3 and InsP6 can activate CIS [1]. </font>

<font size="2"><font face="Georgia">PLC promotes the pathway from ABA to Ca<sup>2+</sup> through InsP3 activating CIS [1,4]. </font><font face="Georgia">Both InsP3 and InsP6 can induce Ca<span style="vertical-align: 6pt;">2+ </span>release [5]. InsP6-caused Ca<span style="vertical-align: 6pt;">2+\r\n</span>release from intracellular stores is not Ca<span style="vertical-align: 6pt;">2+ </span>dependent [6], and elicits a different type of\r\nCa<span style="vertical-align: 6pt;">2+ </span>increase compared to InsP3.However, the InsP3 and InsP6 pathways are\r\nbiochemically linked [7], so we model their synergy as an ?and? function. The ?or?\r\nfunction between the cGMP/cADPR and Ins3/Ins6 pathways reflects the assumption that\r\neach of these pathways can efficiently induce Ca<span style="vertical-align: 6pt;">2+ </span>increase inside the cell [1]. </font></font>

<font face="Georgia" size="2">cGMP promotes the pathway from NO to Ca<sup>2+ </sup>by activating CIS [1,2]. In guard cells, multiple intracellular compartments are able to store Ca<span style="vertical-align: 6pt;">2+ </span>and release it\r\nafter stimulation. The ?and? function between cGMP and cADPR reflects that these two signaling molecules are dependent and may cause Ca<span style="vertical-align: 6pt;">2+ </span>release from the same\r\ncompartment [1,5]. </font>

<font face="Georgia" size="2">cADPR promotes CIS [1,2]. </font><span style="font-family: Georgia; font-size: small;">In guard cells, multiple intracellular compartments are able to store Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">and release it after stimulation. The ?and? function between cGMP and cADPR reflects that these two </span><span style="font-family: Georgia; font-size: small;">signaling molecules are dependent and may cause Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">release from the same compartment [1,5]. </span>

<font face="Georgia" size="2">InsP6 promotes CIS [1,3]. </font><span style="font-family: Georgia; font-size: small;">Both InsP3 and InsP6 can induce Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+</span><span style="font-family: Georgia; font-size: small;">release [5]. InsP6-caused Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">release from intracellular stores is not Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">dependent [6], and elicits a different type of Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">increase compared to InsP3.</span><span style="font-family: Georgia; font-size: small;">However, the InsP3 and InsP6 pathways are biochemically linked [7], so we model their synergy as an ?and? function. The ?or? function between the cGMP/cADPR and Ins3/Ins6 pathways reflects the assumption that each of these pathways can efficiently induce Ca</span><span style="font-family: Georgia; font-size: small; vertical-align: 6pt;">2+ </span><span style="font-family: Georgia; font-size: small;">increase inside the cell [1]. </span>

S_24 1 S_12 1 S_23 1 S_34 1

<font face="Georgia" size="2">GPA1 activates AGB1 [1]. </font>

<font face="Georgia" size="2">GPA1 promotes the conversion from S1P to anionEM by activating AGB1 [1,2,3]. </font>

S_10 1

<font face="Georgia" size="2">OST1, pH, and ROP2 are all required to activate Atrboh. ABI1 inhibits atrboh and is dominant over all activators [1]. </font>

<font face="Georgia" size="2">ABI1 inhibits the progression from ABA to ROS at atrboh [1,2,3]. </font>

<font face="Georgia" size="2">pH changes promotes the change from ABA to closure by promoting the Atrboh [1,5,6]. </font>

<font face="Georgia" size="2">OST1 promotes the progression from ABA to ROS at atrboh [1,4]. </font>

<font face="Georgia" size="2">ROP2 promotes ROS via Atrboh [1,7]. </font>

S_7 1 S_21 1 S_36 1 S_16 1

<font face="Georgia" size="2">PLC activation requires both ABA and Ca<sup>2+ </sup>[1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">PLC-catalyzed InsP3 production requires\r\nCa<span style="vertical-align: 6pt;">2+ </span>[1,3]. </font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ABA induces InsP3 production in guard cells through the PLC pathway [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_29 1 S_14 1

<span style="font-family: Georgia; font-size: small;">SphK produces S1P [1]. </span>

\r\n \r\n \r\n \r\n <div class="page" title="Page 1">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">SphK produces S1P [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_6 1