A limited number of signalling pathways are involved in the specification of cell fate during the development of all animals. Several of these pathways were originally identified in Drosophila. To clarify their roles, and possible cross-talk, we have built a logical model for the nine key signalling pathways recurrently used in metazoan development. In each case, we considered the associated ligands, receptors, signal transducers, modulators, and transcription factors reported in the literature. Implemented using the logical modelling software GINsim, the resulting models qualitatively recapitulate the main characteristics of each pathway, in wild type as well as in various mutant situations (e.g. loss-of-function or gain-of-function). These models constitute pluggable modules that can be used to assemble comprehensive models of complex developmental processes. Moreover, these models of Drosophila pathways could serve as scaffolds for more complicated models of orthologous mammalian pathways. Comprehensive model annotations and GINsim files are provided for each of the nine considered pathways. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2015-01-21T15:24:47Z 2016-01-22T07:08:46Z

Rasp likely palmitoylates&nbsp;<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9VZU2" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(222, 239, 245);">Q9VZU2</a></div><div>Gene Name: rasp</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">44098</span></div>

 2015-12-19T22:41:05Z

Interference Hog (IHOG)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9VM64" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q9VM64</a></div><div>Gene Name: ihog</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">&nbsp;</span><span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">33972</span></div>

 2015-12-19T22:41:05Z

Protein Shifted (Shf)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9W3W5" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(222, 239, 245);">Q9W3W5</a></div><div>Gene Name: shf</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">31617</span></div>

 2015-12-19T22:41:05Z

Protein kinase A<div>UniProt ID:&nbsp;<a style="color: rgb(64, 148, 180); line-height: 20.08px; font-family: Verdana, Arial, sans-serif; font-size: 13.05px; text-decoration: none; border-bottom-width: 0px; cursor: pointer; background-color: rgb(255, 255, 255);" href="http://www.uniprot.org/uniprot/P12370">P12370</a></div><div>Gene Name:&nbsp;<a style="color: rgb(100, 42, 143); line-height: 17.99px; font-family: arial, helvetica, clean, sans-serif; font-size: 13px; white-space: nowrap; background-color: rgb(213, 222, 227);" href="http://www.ncbi.nlm.nih.gov/gene/34284" ref="ordinalpos=4&amp;ncbi_uid=34284&amp;link_uid=34284"><span class="highlight">Pka</span>-C1</a></div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);">34284</span></div><div><span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);"></span>&nbsp;</div><div><span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);"><table style="width: 723pt; border-collapse: collapse;" border="0" cellSpacing="0" cellPadding="0" width="964">\r\n <colgroup><col style="width: 723pt; mso-width-source: userset; mso-width-alt: 30848;" width="964">\r\n <tbody><tr style="height: 15pt;" height="20">\r\n\r\n <td style="border: 0px black; width: 723pt; height: 15pt; background-color: transparent;" class="xl65" height="20" width="964"><font color="#000000" size="3" face="Calibri">protein\r\n kinase, cAMP-dependent, catalytic, alpha</font></td>\r\n\r\n </tr>\r\n</tbody></table></span></div>

 2015-12-19T22:41:05Z

Brother of iHog (BOI)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9W4Y6" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q9W4Y6</a></div><div>Gene Name: boi</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">31229</span></div>

 2015-12-19T22:41:05Z

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; background-color: rgb(255, 255, 255);"><span id="parentSpecies:viewSpeciesDescription">Casein kinase I alpha</span></p><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P54367" style="outline: none; color: rgb(64, 148, 180); text-decoration: none; border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(222, 239, 245);">P54367</a></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">Gene Name:&nbsp;<a href="http://www.ncbi.nlm.nih.gov/gene/32221" ref="ordinalpos=1&amp;ncbi_uid=32221&amp;link_uid=32221" style="outline: none; color: rgb(100, 42, 143); font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17.9998016357422px; white-space: nowrap; background-color: rgb(213, 222, 227);">CkIalpha</a></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">32221</span></div>

 2015-12-19T22:41:05Z

Protein Kinase Shaggy (Sgg)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q6A4W4" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q6A4W4</a></div><div>Gene Name: Sgg</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">31248</span></div>

 2015-12-19T22:41:05Z

Target of Wingless (TOW)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/A8JNM0" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">A8JNM0</a></div><div>Gene Name: tow</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">38755</span></div>

 2015-12-19T22:41:05Z

lipid-transferring molecule Lipophorin<div><br/></div>

 2015-12-19T22:41:05Z

Tout-velu (TTV), a heparan sulphate\r\ncopolymerase<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9V730" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q9V730</a></div><div>Gene Name: ttv</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">36614</span></div>

 2015-12-19T22:41:05Z

Dispatched (Disp) transmembrane protein [fruit fly]<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9VNJ5" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(222, 239, 245);">Q9VNJ5</a>&nbsp;</div><div>Gene Name: disp</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">44274</span></div>

 2015-12-19T22:41:05Z

G protein receptor-coupled kinase 2 (GPRK2)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P32866" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P32866</a></div><div>Gene Name: Gprk2</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">49045</span></div>

 2015-12-19T22:41:05Z

F-box protein Supernumary limbs (SLMB)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q9VDE3" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q9VDE3</a><br/>Gene Name: slmb</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">42504</span><span style="font-size: 10pt;">&nbsp;</span></div>

 2015-12-19T22:41:05Z

Kinesin-like protein Costa (COS)&nbsp;<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/O16844" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">O16844</a></div><div>Gene Name: cos</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">35653</span></div>

 2015-12-19T22:41:05Z

Smoothened (SMO)<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q29NW6" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q29NW6</a></div><div>Gene Name: smo</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">33196</span></div>

 2015-12-19T22:41:05Z

Patched (ptc) membrane protein<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P18502" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(222, 239, 245);">P18502</a></div><div>Gene Name: ptc</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">35851</span></div>

 2015-12-19T22:41:05Z

Suppressor of Fused protein<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/W8C1N7" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">W8C1N7</a></div><div>Gene Name: SUFU</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">51684</span></div>

 2015-12-19T22:41:05Z

Target nodes from the paper [1]

 2015-12-19T22:41:05Z

Hedgehog (HH) segment polarity gene<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q02936" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q02936</a></div><div>Gene Name: hh</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">42737</span></div>

 2015-12-19T22:41:05Z

Division Abnormally Delayed&nbsp;proteglycans<div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;">UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/Q966V5" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q966V5</a></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;">Gene Name: dally</div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;">Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">39013</span></div>

 2015-12-19T22:41:05Z

Dally-like proteoglycans&nbsp;<span style="font-size: 13.3333330154419px;">(DLP)</span><div><span style="font-size: 13.3333330154419px;">UniProt ID:&nbsp;</span><a href="http://www.uniprot.org/uniprot/Q9GPL5" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">Q9GPL5</a></div><div><span style="font-size: 13.3333330154419px;">Gene Name: dlp</span></div><div><span style="font-size: 13.3333330154419px;">Gene ID:&nbsp;</span><span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">39596</span></div>

 2015-12-19T22:41:05Z

Fused (FU) Segment Polarity Gene<div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P23647" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P23647</a></div><div>Gene Name: fu</div><div>Gene ID:&nbsp;<span style="font-size: 10pt;">&nbsp;</span><span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">32855</span></div>

 2015-12-19T22:41:05Z

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; background-color: rgb(255, 255, 255);"><span id="parentSpecies:viewSpeciesDescription">Cubitus Interruptus (CI) activator</span></p><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">Info for CI (fruit fly):</div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P19538" style="outline: none; color: rgb(64, 148, 180); text-decoration: none; border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px;">P19538</a></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">Gene Name: ci</div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);">Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">43767</span></div>

 2015-12-19T22:41:05Z

Cubitus Interruptus (CI) repressor<div>Info for CI (fruit fly):</div><div>UniProt ID:&nbsp;<a href="http://www.uniprot.org/uniprot/P19538" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P19538</a></div><div>Gene Name: ci</div><div>Gene ID:&nbsp;<span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">43767</span></div>

 2015-12-19T22:41:05Z

Fu inhibits Cos [1, 2]. Smo<span style="font-size: 13.3333330154419px;">&nbsp;inhibits Cos [1, 3, 4, 5, 6, 7, 8, 9, 10].&nbsp;</span>

"In the absence of HH binding, FU and COS are basally\r\nphosphorylated and, together with CI, form a complex\r\nsequestered on microtubules. In the presence of HH binding, FU and COS are hyperphosphorylated,\r\nthereby weakening their binding to\r\nmicrotubules" [1, 2]

"In the presence of HH, COS forms a complex with SMO" [1, 2, 3, 4, 5, 6, 7, 8, 9]

 S_18 1 S_5 1

Gprk2 positively regulates SMO [1, 3]. Tow and Ptc inhibit SMO [1, 2, 4].

"The activity of Smoothened (SMO) is regulated by the\r\ntransmembrane protein Patched (PTC)" [1, 2]

"G protein receptor-coupled kinase 2 (GPRK2)\r\nparticipates in the Hedgehog (HH) pathway, likely by\r\ncontributing to SMO protein phosphorylation in response\r\nto HH" [1, 3]

"PTC repression of SMO is tentatively mediated by TOW,\r\npossibly through regulation of the degradation or\r\nhomeostasis of lipophorin particles, thereby controlling\r\nthe availability of SMO ligand(s)" [1, 3]<br/>

 S_22 1 S_7 1 S_15 1

<span style="font-size: 13.3333330154419px;">Hh inhibits ptc [1]</span>

Hh inhibits ptc [1]

 S_13 1

Fu inhibits SuFu [1, 2]

SU(FU) is phosphorylated by FU in response to HH\r\nsignalling [1, 2]

 S_18 1

Ci_act activates Targets, while Ci_rep inhibits them [1, 2].

Pathway activation is mediated by the full-length CI\r\nmolecule CI-act [1, 2]

"Repressor CI activity is mediated by an N-terminal\r\nprotein fragment CI-rep lacking the carboxy regulatory\r\ndomain" [1, 2]

 S_20 1 S_24 1

Dlp, Boi, Dally, iHOG, Lipophorin, Rasp, Shf [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11] in conjunction activate Hh.

"Brother of iHog (BOI), like IHOG, functions as a\r\nreceptor for Hedgehog (HH).\r\nBOI is a member of a larger family of HH-binding\r\nproteins that includes IHOG" [1, 5]

"shifted (shf) mutations decrease the range and level of\r\nHH signaling...SHF is required for normal range of movement of\r\ncholesterol modified HH in the wing disc.\r\nSecreted SHF controls the stability (accumulation) and\r\nmovement of HH through direct interaction with HH." [1, 10, 11]

The protein encoded by HH is modified by cholesterol on the\r\nC-terminus and palmitoylated on a cysteine near the Nterminus. This dually lipidated molecule requires the action of\r\nDispatched (Disp) for release from the cell membrane [1, 4]

"Interference Hog (IHOG) is a receptor for Hedgehog\r\n(HH) that facilitates the binding\r\nof HH to Patched (PTC)." [1, 9]&nbsp;

"Movement to neighboring cells likely involves the\r\nglypican family member Dally-like (Dlp)" [1, 2, 3].

"The heparan sulfate proteoglycanDivision Abnormally\r\nDelayed (DALLY) and Dally-like (DLP) are the\r\nsubstrates for TTV and are involved in HH signalling" [1, 6]

"Lipophorins are lipid-transporting particles that are\r\nimportant for Hedgehog (HH) movement.\r\nLipophorins form a complex with HH and membrane\r\nassociated and solubilized glypican family members.\r\nInteractions between lipophorins and the glypicans are\r\nmediated by the heparan sulfate moieties found on\r\nglypicans, and these interactions are likely important to\r\nHH movement." [1, 7]

"Skinny Hedgehog or Rasp likely palmitoylates Hedgehog\r\n(HH), a modification essential for its activity." [1, 8]

 S_3 1 S_8 1 S_4 1 S_21 1 S_16 1 S_14 1 S_17 1 S_1 1

Ttv positively regulates Dally [1, 2]

Dally is a substrate for Ttv [1, 2]

 S_19 1

Ttv positively regulates Dlp [1, 2].

Dlp is a substrate of Ttv [1, 2]

 S_19 1

Smo positively regulates Fu [1, 2, 3, 4].

SMO recruits\r\na large cytoplasmic complex to its cytoplasmic tail that\r\ncontains COS, FU, and CI [1, 2, 3, 4]&nbsp;

 S_5 1

CK1a, Cos, Pka, Sgg, Slmb, and SuFu in conjunction inhibit Ci_act [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]

<span style="font-size: 13.3333330154419px;">"CI directly binds to the other HH pathway components COS and SU(FU)" [1, 2, 3, 4, 5, 6]</span>

"Phosphorylation by PKA primes both SMO and CI for\r\nsubsequent CK1a phosphorylation." [1]&nbsp;<div><span style="font-size: 13.3333330154419px;">"</span><span style="font-size: 10pt;">Zeste white 3 or Shaggy (Sgg), functions in concert with the protein kinase A (PKA) and casein kinase 1a (CK1a) to promote the phorphorylation of CI" [1, 8, 9]</span></div>

"CI phosphorylation enables the\r\nrecruitment of SLMB, resulting in CI\r\nubiquitinylation and its proteasome-mediated proteolytic\r\nprocessing into a repressor" [1, 10, 11, 12]

<span style="font-size: 13.3333330154419px;">"Phosphorylation by PKA primes both SMO and CI for subsequent CK1a phosphorylation." [1]&nbsp;</span><div><span style="font-size: 13.3333330154419px;">"</span><span style="font-size: 10pt;">Zeste white 3 or Shaggy (Sgg), functions in concert with\r\nthe protein kinase A (PKA) and casein kinase 1a (CK1a)\r\nto promote the phorphorylation of CI" [1, 8, 9]</span></div>

"CI directly binds to the other HH pathway components\r\nCOS and SU(FU)" [1, 2, 3, 4, 5, 6]

<span style="font-size: 13.3333330154419px;">"</span><span style="font-size: 10pt;">Zeste white 3 or Shaggy (Sgg), functions in concert with the protein kinase A (PKA) and casein kinase 1a (CK1a) to promote the phorphorylation of CI" [1, 8, 9]</span>

 S_2 1 S_9 1 S_23 1 S_10 1 S_6 1 S_12 1

CK1a and Cos and Pka and Sgg and Slmb and Sufu work in conjunction to positively regulate Ci_rep [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]

"CI directly binds to the other HH pathway components COS and Su(FU)" [1, 9, 10]

"Proteolysis of CI is initiated by phosphorylation by the\r\nprotein kinases PKA, SGG and CK1a" [1, 2, 3, 4]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">"CI phosphorylation enables the recruitment of SLMB, resulting in CI ubiquitinylation and its proteasome-mediated proteolytic processing into a repressor" [1, 11, 12, 13]</span>

<span style="font-size: 13.3333330154419px;">"Proteolysis of CI is initiated by phosphorylation by the protein kinases PKA, SGG and CK1a" [1, 2, 3, 4]</span>

<span style="font-size: 13.3333330154419px;">"CI directly binds to the other HH pathway components COS and Su(FU)"</span>&nbsp;[1, 5, 6, 7, 8]

<span style="font-size: 13.3333330154419px;">"Proteolysis of CI is initiated by phosphorylation by the protein kinases PKA, SGG and CK1a" [1, 2, 3, 4]</span>

 S_10 1 S_9 1 S_23 1 S_6 1 S_2 1 S_12 1