KEGG   PATHWAY: oaa04340
Entry
oaa04340                    Pathway                                
Name
Hedgehog signaling pathway - Ornithorhynchus anatinus (platypus)
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
oaa04340  Hedgehog signaling pathway
oaa04340

Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
100079214  PTCH1; protein patched homolog 1 isoform X2 [KO:K06225]
103167620  PTCH2; protein patched homolog 2 [KO:K11101]
100078770  SMO; smoothened homolog [KO:K06226]
100083316  GPR161; G-protein coupled receptor 161 [KO:K08439]
100078846  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100088079  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
100076676  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
100092471  CSNK1G2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
100077880  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
100075995  CSNK1G3; casein kinase I isoform X3 [KO:K08958] [EC:2.7.11.1]
100088374  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
100090166  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
100092089  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100081663  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
100075383  GLI3; LOW QUALITY PROTEIN: transcriptional activator GLI3 [KO:K06230]
100080715  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
100076130  KIF7; kinesin-like protein KIF7 [KO:K18806]
100082746  LOW QUALITY PROTEIN: hedgehog-interacting protein [KO:K06231]
100075081  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100088940  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
114807635  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100073945  CUL1; cullin-1 [KO:K03347]
100076818  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
100080584  BTRC; F-box/WD repeat-containing protein 1A isoform X3 [KO:K03362]
100078192  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
100090098  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
100081692  SHH; sonic hedgehog protein [KO:K11988]
114811996  IHH; indian hedgehog protein [KO:K11989]
100080014  DHH; desert hedgehog protein [KO:K11990]
100076153  DISP1; protein dispatched homolog 1 isoform X1 [KO:K24680]
100079390  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
100082574  BOC; brother of CDO isoform X4 [KO:K20020]
100087042  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
114807931  GAS1; growth arrest-specific protein 1 [KO:K06232]
100083379  LRP2; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
100680814  MOSMO; modulator of smoothened protein [KO:K23663]
100085452  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
100086500  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
100079802  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
100081555  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100090102  GRK2; LOW QUALITY PROTEIN: beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
100078284  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
103168574  EVC; ellis-van Creveld syndrome protein [KO:K19605]
100077378  EVC2; limbin [KO:K19608]
100087751  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
100082726  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
100086715  ARRB1; beta-arrestin-1 [KO:K04439]
100084244  ARRB2; beta-arrestin-2 [KO:K04439]
100079749  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
100081761  CUL3; cullin-3 [KO:K03869]
100079377  SPOPL; speckle-type POZ protein-like [KO:K10523]
100093443  speckle-type POZ protein [KO:K10523]
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
oaa04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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