Hedgehog Signaling Pathway Netpath (Homo sapiens)

From WikiPathways

Jump to: navigation, search
Protein-protein dissociationEndosomesHedgehog Signaling PathwayCiliaGLI2STK36STK36GLI1ADRBK1ARRB2SMOIHHSUFUSAP18GLI1DHHPTCH1PTCH2SHHGLI2GLI3DHHSUFUKIF7IHHSHHGLI3SIN3ASMOCYNUCYNUPMENProteinInhibitionAuto 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.

Quality Tags

Ontology Terms

 

Bibliography

No bibliography


History

View all...
CompareRevisionActionTimeUserComment
107440view07:03, 8 October 2019DeSlModified title
78542view10:30, 7 January 2015MaintBotadded missing graphIds
70092view18:32, 12 July 2013MaintBotupdating to 2013 schema
47979view14:40, 23 April 2012NetPathModified description
45345view20:25, 7 October 2011AlexanderPicoOntology Term : 'Hedgehog signaling pathway' added !
44831view07:39, 6 October 2011Mkutmonconnected some lines
44830view07:38, 6 October 2011Mkutmonconnected some lines
44618view17:44, 22 September 2011KhanspersAdded category
44617view17:43, 22 September 2011KhanspersUpdating content to NetSlim
44115view20:42, 24 August 2011KhanspersReverted to version '23:43, 1 March 2011' by Khanspers
44039view23:26, 22 August 2011KhanspersModified description
44038view23:25, 22 August 2011KhanspersUpdating pathway from NetSlim
41187view23:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
35650view21:41, 12 February 2010KhanspersModified description
35632view19:08, 12 February 2010AndraAdded references
20775view11:29, 14 November 2008MaintBot[[Pathway:Homo sapiens:Hedgehog Netpath 10]] moved to [[Pathway:WP47]]: Moved to stable identifier
14140view14:47, 21 May 2008Andraexercise
8126view13:46, 7 January 2008MaintBot[[Pathway:Human:Hedgehog Netpath 10]] moved to [[Pathway:Homo sapiens:Hedgehog Netpath 10]]: Renaming species
7684view16:09, 18 December 2007MaintBotfixed category names
7235view12:41, 4 November 2007MaintBotAdded categories to GPML
6331view22:17, 22 May 2007A.Pandeygpml file for [[Human:Hedgehog_Netpath_10]]

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADRBK1Protein156 (Entrez Gene)
ARRB2Protein406 (Entrez Gene)
DHHProtein50846 (Entrez Gene)
GLI1Protein2735 (Entrez Gene)
GLI2Protein2736 (Entrez Gene)
GLI3Protein2737 (Entrez Gene)
IHHProtein3549 (Entrez Gene)
KIF7Protein374654 (Entrez Gene)
PTCH1Protein5727 (Entrez Gene)
PTCH2Protein8643 (Entrez Gene)
SAP18Protein10284 (Entrez Gene)
SHHProtein6469 (Entrez Gene)
SIN3AProtein25942 (Entrez Gene)
SMOProtein6608 (Entrez Gene)
STK36Protein27148 (Entrez Gene)
SUFUProtein51684 (Entrez Gene)

Annotated Interactions

No annotated interactions

Personal tools