KEGG   PATHWAY: bta04340
Entry
bta04340                    Pathway                                
Name
Hedgehog signaling pathway - Bos taurus (cow)
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
bta04340  Hedgehog signaling pathway
bta04340

Organism
Bos taurus (cow) [GN:bta]
Gene
100138998  [KO:K08957] [EC:2.7.11.1]
100335574  MOSMO; modulator of smoothened protein isoform X1 [KO:K23663]
100336796  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678]
100337021  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
112446327  [KO:K03347]
280834  EVC2; limbin [KO:K19608]
281020  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
281637  ARRB1; beta-arrestin-1 [KO:K04439]
281638  ARRB2; beta-arrestin-2 [KO:K04439]
282136  GRK3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
282322  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
282323  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
282682  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
282684  CSNK1A1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
282874  EVC; evC complex member EVC [KO:K19605]
286821  SHH; sonic hedgehog protein [KO:K11988]
407190  CSNK1G3; casein kinase I isoform gamma-3 [KO:K08958] [EC:2.7.11.1]
407228  CUL1; cullin-1 [KO:K03347]
505160  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
506060  CSNK1G2; casein kinase I isoform gamma-2 [KO:K08958] [EC:2.7.11.1]
507948  PTCH2; protein patched homolog 2 isoform X2 [KO:K11101]
510255  GLI2; zinc finger protein GLI2 [KO:K16798]
510817  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
512018  BOC; brother of CDO precursor [KO:K20020]
513902  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X3 [KO:K04678] [EC:2.3.2.26]
516072  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
517588  GLI1; zinc finger protein GLI1 [KO:K16797]
520994  PTCH1; protein patched homolog 1 [KO:K06225]
522714  IHH; indian hedgehog protein [KO:K11989]
523542  CSNK1D; casein kinase I isoform delta [KO:K08959] [EC:2.7.11.1]
524530  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
525833  DHH; desert hedgehog protein [KO:K11990]
527889  CSNK1G1; casein kinase I isoform gamma-1 [KO:K08958] [EC:2.7.11.1]
529930  [KO:K10604] [EC:2.3.2.27]
529947  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X4 [KO:K24706]
530618  SPOP; speckle-type POZ protein [KO:K10523]
534072  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
534325  CUL3; cullin-3 [KO:K03869]
535067  SUFU; suppressor of fused homolog [KO:K06229]
536011  CDON; cell adhesion molecule-related/down-regulated by oncogenes precursor [KO:K20033]
538808  KIF7; kinesin-like protein KIF7 isoform X4 [KO:K18806]
539308  SMO; protein smoothened precursor [KO:K06226]
540336  GAS1; growth arrest-specific protein 1 [KO:K06232]
540642  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
540826  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
540830  HHIP; hedgehog-interacting protein precursor [KO:K06231]
541246  KIF3A; kinesin-like protein KIF3A [KO:K10394]
613515  [KO:K08957] [EC:2.7.11.1]
615414  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
615688  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
616130  MGRN1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
618833  IQCE; IQ domain-containing protein E isoform X8 [KO:K24677]
768006  GPR161; G protein-coupled receptor 161 [KO:K08439]
768234  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
785371  GLI3; transcriptional activator GLI3 isoform X3 [KO:K06230]
785423  CSNK1B; casein kinase I isoform beta [KO:K08957] [EC:2.7.11.1]
790875  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
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
bta04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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