KEGG   PATHWAY: hmh04340
Entry
hmh04340                    Pathway                                
Name
Hedgehog signaling pathway - Hylobates moloch (silvery gibbon)
Description
The Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for transduction of the Hedgehog signal in vertebrates. In Hh's absence, the Ptch receptor localizes to the cilium, where it inhibits Smo activation. Gli proteins are phosphorylated by PKA, CKI and GSK3B and partially degraded into truncated Gli repressor form (GliR) that suppresses Hh target gene transcription in the nucleus. In Hh's presence, Ptch disappears from the cilium, and activated Smo contributes to the translocation of the protein complex Gli, Sufu, Kif7 to ciliary tip, where Gli dissociates from the negative regulator Sufu. The production of Gli activator form (GliA) occurs and the increased nuclear accumulation of GliA results in activation transcription of Hh target genes.
Class
Environmental Information Processing; Signal transduction
Pathway map
hmh04340  Hedgehog signaling pathway
hmh04340

Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116456774  EVC2; limbin [KO:K19608]
116456775  EVC; evC complex member EVC [KO:K19605]
116457608  DISP1; protein dispatched homolog 1 [KO:K24680]
116457652  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X2 [KO:K24678]
116457794  EFCAB7; EF-hand calcium-binding domain-containing protein 7 isoform X1 [KO:K23852]
116458418  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
116459229  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
116459253  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
116459283  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
116459388  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
116461670  DHH; desert hedgehog protein [KO:K11990]
116462283  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
116462900  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
116462943  GLI2; zinc finger protein GLI2 [KO:K16798]
116464499  HHIP; hedgehog-interacting protein [KO:K06231]
116466895  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116466943  BOC; brother of CDO isoform X1 [KO:K20020]
116467072  CSNK1A1L; casein kinase I [KO:K08957] [EC:2.7.11.1]
116468493  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
116469070  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
116469117  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
116469844  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116470834  KIF3A; kinesin-like protein KIF3A isoform X2 [KO:K10394]
116470866  [KO:K03347]
116470882  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
116471123  MOSMO; modulator of smoothened protein [KO:K23663]
116471700  CSNK1A1; casein kinase I isoform X3 [KO:K08957] [EC:2.7.11.1]
116471847  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
116472548  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
116473075  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
116473275  GPR161; G-protein coupled receptor 161 [KO:K08439]
116473600  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X2 [KO:K24679]
116474663  SPOP; speckle-type POZ protein [KO:K10523]
116475208  GAS1; growth arrest-specific protein 1 [KO:K06232]
116475280  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
116476535  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
116476694  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
116477142  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X2 [KO:K20033]
116478588  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116480600  MEGF8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
116480865  GLI1; zinc finger protein GLI1 [KO:K16797]
116481802  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
116482419  CSNK1G1; casein kinase I isoform X2 [KO:K08958] [EC:2.7.11.1]
116483912  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
116484020  CSNK1G2; casein kinase I isoform X2 [KO:K08958] [EC:2.7.11.1]
116484211  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
116484796  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
116809362  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
116809459  IHH; indian hedgehog protein [KO:K11989]
116809539  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
116810179  CUL3; cullin-3 isoform X1 [KO:K03869]
116810813  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
116810891  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
116812519  GLI3; transcriptional activator GLI3 [KO:K06230]
116814346  SMO; protein smoothened isoform X1 [KO:K06226]
116814485  CUL1; cullin-1 [KO:K03347]
Compound
C00575  3',5'-Cyclic AMP
Reference
PMID:26875496
  Authors
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
  Title
Hedgehog receptor function during craniofacial development.
  Journal
Dev Biol 415:198-215 (2016)
DOI:10.1016/j.ydbio.2016.02.009
Reference
PMID:23719536
  Authors
Briscoe J, Therond PP
  Title
The mechanisms of Hedgehog signalling and its roles in development and disease.
  Journal
Nat Rev Mol Cell Biol 14:416-29 (2013)
DOI:10.1038/nrm3598
Reference
PMID:26077918
  Authors
Alman BA
  Title
The role of hedgehog signalling in skeletal health and disease.
  Journal
Nat Rev Rheumatol 11:552-60 (2015)
DOI:10.1038/nrrheum.2015.84
Reference
PMID:26064136
  Authors
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
  Title
Hedgehog and Resident Vascular Stem Cell Fate.
  Journal
Stem Cells Int 2015:468428 (2015)
DOI:10.1155/2015/468428
Reference
PMID:23799571
  Authors
Sasai N, Briscoe J
  Title
Primary cilia and graded Sonic Hedgehog signaling.
  Journal
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
DOI:10.1002/wdev.43
Reference
PMID:20708941
  Authors
Heretsch P, Tzagkaroulaki L, Giannis A
  Title
Modulators of the hedgehog signaling pathway.
  Journal
Bioorg Med Chem 18:6613-24 (2010)
DOI:10.1016/j.bmc.2010.07.038
Reference
PMID:22534646
  Authors
Anderson E, Peluso S, Lettice LA, Hill RE
  Title
Human limb abnormalities caused by disruption of hedgehog signaling.
  Journal
Trends Genet 28:364-73 (2012)
DOI:10.1016/j.tig.2012.03.012
Reference
PMID:18583599
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
PMID:24925320
  Authors
Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY
  Title
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.
  Journal
Elife 3:e02555 (2014)
DOI:10.7554/eLife.02555
Reference
PMID:22056910
  Authors
Ok CY, Singh RR, Vega F
  Title
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
  Journal
Am J Pathol 180:2-11 (2012)
DOI:10.1016/j.ajpath.2011.09.009
Reference
PMID:26366162
  Authors
Hsia EY, Gui Y, Zheng X
  Title
Regulation of Hedgehog signaling by ubiquitination.
  Journal
Front Biol (Beijing) 10:203-220 (2015)
DOI:10.1007/s11515-015-1343-5
Reference
PMID:29290584
  Authors
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
  Title
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
  Journal
Dev Cell 44:113-129.e8 (2018)
DOI:10.1016/j.devcel.2017.12.003
Reference
PMID:24582806
  Authors
Pusapati GV, Hughes CE, Dorn KV, Zhang D, Sugianto P, Aravind L, Rohatgi R
  Title
EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.
  Journal
Dev Cell 28:483-96 (2014)
DOI:10.1016/j.devcel.2014.01.021
Reference
PMID:27779865
  Authors
Rodgers UR, Lanyon-Hogg T, Masumoto N, Ritzefeld M, Burke R, Blagg J, Magee AI, Tate EW
  Title
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
  Journal
ACS Chem Biol 11:3256-3262 (2016)
DOI:10.1021/acschembio.6b00896
Related
pathway
hmh04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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