KEGG   PATHWAY: oga04340
Entry
oga04340                    Pathway                                
Name
Hedgehog signaling pathway - Otolemur garnettii (small-eared galago)
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
oga04340  Hedgehog signaling pathway
oga04340

Organism
Otolemur garnettii (small-eared galago) [GN:oga]
Gene
100961156  PTCH1; protein patched homolog 1 isoform X2 [KO:K06225]
100941318  PTCH2; protein patched homolog 2 [KO:K11101]
100954610  SMO; smoothened homolog [KO:K06226]
100960555  GPR161; G-protein coupled receptor 161 isoform X1 [KO:K08439]
100964083  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
100966533  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100961078  casein kinase I-like isoform X1 [KO:K08957] [EC:2.7.11.1]
100942799  CSNK1A1L; casein kinase I [KO:K08957] [EC:2.7.11.1]
100963051  casein kinase I-like isoform X1 [KO:K08957] [EC:2.7.11.1]
100964686  casein kinase I-like [KO:K08957] [EC:2.7.11.1]
100953920  CSNK1A1; casein kinase I isoform X3 [KO:K08957] [EC:2.7.11.1]
100954567  CSNK1G1; casein kinase I [KO:K08958] [EC:2.7.11.1]
100960115  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
100941753  CSNK1G2; casein kinase I isoform X2 [KO:K08958] [EC:2.7.11.1]
100963495  CSNK1D; casein kinase I [KO:K08959] [EC:2.7.11.1]
100948365  CSNK1E; casein kinase I isoform X3 [KO:K08960] [EC:2.7.11.1]
100952751  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100954193  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
100950930  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
100947812  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
100960983  SUFU; suppressor of fused homolog isoform X2 [KO:K06229]
100956697  KIF7; kinesin-like protein KIF7 [KO:K18806]
100950417  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
100958947  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100962188  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100955447  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100962270  CUL1; cullin-1 [KO:K03347]
100942812  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
100946977  FBXW11; F-box/WD repeat-containing protein 11 isoform X2 [KO:K03362]
100956434  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X2 [KO:K24678] [EC:2.3.1.-]
100943573  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
100946098  SHH; sonic hedgehog protein [KO:K11988]
100946168  IHH; indian hedgehog protein [KO:K11989]
100945480  DHH; desert hedgehog protein [KO:K11990]
100944519  DISP1; protein dispatched homolog 1 [KO:K24680]
100962093  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X2 [KO:K24706]
100956729  BOC; brother of CDO isoform X1 [KO:K20020]
100955355  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X5 [KO:K20033]
100947741  GAS1; growth arrest-specific protein 1 [KO:K06232]
100948006  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
100963223  CUNH16orf52; uncharacterized protein C16orf52 homolog [KO:K23663]
100951718  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
100946515  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X2 [KO:K10604] [EC:2.3.2.27]
100955068  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100941546  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
100943694  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
100966357  GRK3; beta-adrenergic receptor kinase 2 isoform X4 [KO:K00910] [EC:2.7.11.15]
100955176  EVC; ellis-van Creveld syndrome protein isoform X2 [KO:K19605]
100954867  EVC2; limbin isoform X1 [KO:K19608]
100941046  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
100957033  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
100946246  ARRB1; beta-arrestin-1 [KO:K04439]
100954933  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
100953501  KIF3A; kinesin-like protein KIF3A [KO:K10394]
100959716  CUL3; cullin-3 [KO:K03869]
100946851  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
100948900  SPOP; 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
oga04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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