KEGG   PATHWAY: pcoq04340
Entry
pcoq04340                   Pathway                                
Name
Hedgehog signaling pathway - Propithecus coquereli (Coquerel's sifaka)
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
pcoq04340  Hedgehog signaling pathway
pcoq04340

Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105805276  [KO:K08960] [EC:2.7.11.1]
105805384  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
105805443  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678]
105806029  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
105806088  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
105806290  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
105806400  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
105806844  PTCH1; protein patched homolog 1 [KO:K06225]
105807940  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105808739  CUL3; cullin-3 [KO:K03869]
105808761  IHH; indian hedgehog protein [KO:K11989]
105808987  HHIP; hedgehog-interacting protein [KO:K06231]
105809842  KIF7; kinesin-like protein KIF7 [KO:K18806]
105810130  DISP1; protein dispatched homolog 1 [KO:K24680]
105810132  CSNK1A1L; casein kinase I isoform alpha-like [KO:K08957] [EC:2.7.11.1]
105810179  ADRBK2; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
105810638  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
105810822  CSNK1G1; casein kinase I isoform gamma-1 isoform X1 [KO:K08958] [EC:2.7.11.1]
105810926  [KO:K23663]
105811149  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105811270  CSNK1G2; casein kinase I isoform gamma-2 [KO:K08958] [EC:2.7.11.1]
105811510  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
105813128  MGRN1; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
105814052  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
105814664  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
105815367  DHH; desert hedgehog protein [KO:K11990]
105815388  SPOPL; speckle-type POZ protein-like [KO:K10523]
105815531  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
105816016  KIF3A; kinesin-like protein KIF3A [KO:K10394]
105816297  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
105816744  BOC; brother of CDO isoform X1 [KO:K20020]
105817702  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
105818206  SHH; sonic hedgehog protein [KO:K11988]
105818447  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
105818502  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
105820035  CSNK1D; casein kinase I isoform delta isoform X1 [KO:K08959] [EC:2.7.11.1]
105821111  GPR161; G-protein coupled receptor 161 isoform X1 [KO:K08439]
105821524  CSNK1A1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
105822396  GAS1; growth arrest-specific protein 1 [KO:K06232]
105822532  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
105822622  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105822880  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
105823839  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105824061  SPOP; speckle-type POZ protein [KO:K10523]
105824339  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
105824358  SUFU; suppressor of fused homolog [KO:K06229]
105824617  CUL1; cullin-1 [KO:K03347]
105825147  EVC2; limbin [KO:K19608]
105825157  EVC; ellis-van Creveld syndrome protein [KO:K19605]
105826135  CDON; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
105826353  CSNK1G3; casein kinase I isoform gamma-3 [KO:K08958] [EC:2.7.11.1]
105826774  SMO; smoothened homolog [KO:K06226]
105827405  ADRBK1; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
105827423  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
Compound
C00575  3',5'-Cyclic AMP
Reference
  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
  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
  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
  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
  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
  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
  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
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
  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
  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
  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
  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
  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
  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
pcoq04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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