Hedgehog Signaling Pathway (Bos taurus)

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Hedgehog Signaling PathwayCiliaProtein-protein dissociationEndosomesSAP18PTCH1SUFUGLI2GLI1IHHGLI3SHHSTK36ARNTLKIF7GLI2SMODHHSHHSTK36IHHDHHADRBK1GLI1SUFUGLI3SIN3APTCH2SMOCYNUCYNUPMENProteinInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavagemRNAReceptorLigandProteinEnzyme complex


Description

The Hedgehog family of proteins are signaling proteins that are crucial for a number of physiological processes including morphogenesis during development. In adult organisms, it is also involved in the regulation of theca cell development in growing follicles and in regulating the development and function of the somatic cells of the testis. Vertebrates are known to have 3 Hedgehog genes, which show different spatio-temporal expression patterns and perform specialized functions. These are - Desert hedgehog (Dhh), Indian hedgehog (Ihh), and Sonic hedgehog (Shh). The Patched (PTCH) proteins (Patched 1 and Patched 2 - PTCH1 and PTCH2) serve as receptors for the Hedgehog proteins. In the 'off' state, PTCH receptors inhibit the Smo protein by mechanism(s) which are still not understood completely. In this state, the Gli2/3 Zn-finger transcription factors are phosphorylated and processed in a proteasome-dependent manner to generate a transcriptionally repressor form. SUFU, a cytoplasmic protein, was also found to interact with all the three Gli proteins resulting in the repression of its transcriptional activity. In the 'Signaling cell', which is the cell which secretes the Hedgehog proteins, an active ligand is produced following processing of the precursor Hedgehog protein. This processing involves autocleavage by the catalytic domain and bi-lipidation (cholesterol moiety at C-terminus and palmitate at the N-terminus) of the Hedgehog protein. These active ligands travel to the 'responding cell' via interactions with glypicans and megalin. On the responding cell, the active ligand interacts with PATCHED 1 (PTCH1) and PATCHED 2 (PTCH2), which results in the activation and translocation of Smoothed (Smo) to the cilium(plasma membrane in Drosophila). Activation of Smo results in the inhibition of Gli proteolysis and the production of the transcriptional repressor form. This might also promote the formation of the transcription activator form of the protein. The G-protein coupled receptor kinase-2 enhances the association between β-arrestin 2 and Smo probably by phosphorylating Smo. The two proteins also mediates increased internalization of Smo in a clathrin- dependent process and increased Hedgehog signaling. Kif7, a Drosophila Costal2 (Cos2) homolog, is capable of interacting with the Gli proteins and is known to exert positive and negative effects on Hedgehog signaling. The Fused (Fu) homolog, which can form a complex with Kif7, Gli and and SuFu (similar to Drosophila Gli, Cos2, Su and SuFu) may also be involved in the regulation of this pathway.


Please access this pathway at NetSlim database.

If you use this pathway, you must cite following paper:

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP47(78542) with a 100.0% conversion rate.

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Ontology Terms

 

Bibliography

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History

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CompareRevisionActionTimeUserComment
111050view12:39, 3 July 2020L DupuisConverted interactions to graphical lines in legend
80656view15:20, 30 June 2015Mkutmonhomology conversion
79162view05:14, 6 March 2015MaintBotUpdated conversion from Hs
67325view10:37, 26 June 2013Christine ChichesterOntology Term : 'Hedgehog signaling pathway' added !
63470view17:19, 10 May 2013MaintBotUpdated to 2013 gpml schema
40606view19:34, 1 March 2011MaintBotRemoved redundant pathway information and comments
35744view23:53, 12 February 2010AlexanderPico
33843view00:33, 9 December 2009MaintBotAutomatic update of empty xrefs
32496view12:47, 17 August 2009MaintBotFixed text labels
31194view19:31, 13 August 2009MaintBotFixed text labels
30591view22:12, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADRBK1ProteinENSBTAG00000005832 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:156
ARNTLProteinENSBTAG00000013029 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:406
DHHProteinENSBTAG00000000124 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:50846
GLI1ProteinENSBTAG00000006631 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2735
GLI2ProteinENSBTAG00000011682 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2736
GLI3ProteinENSBTAG00000010671 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2737
IHHProteinENSBTAG00000008452 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3549
KIF7ProteinENSBTAG00000002440 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:374654
PTCH1ProteinENSBTAG00000048213 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5727
PTCH2ProteinENSBTAG00000024137 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8643
SAP18ProteinENSBTAG00000018631 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10284
SHHProteinENSBTAG00000024552 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6469
SIN3AProteinENSBTAG00000009985 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25942
SMOProteinENSBTAG00000013287 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6608
STK36ProteinENSBTAG00000003819 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27148
SUFUProteinENSBTAG00000021068 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51684

Annotated Interactions

No annotated interactions
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