KEGG   PATHWAY: ray04340
Entry
ray04340                    Pathway                                
Name
Hedgehog signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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
ray04340  Hedgehog signaling pathway
ray04340

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107497056  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
107497788  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
107498940  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
107498977  CSNK1G2; casein kinase I [KO:K08958] [EC:2.7.11.1]
107499070  CUL3; cullin-3 isoform X1 [KO:K03869]
107499374  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
107499745  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
107500535  CUL1; cullin-1 isoform X1 [KO:K03347]
107501496  GLI1; zinc finger protein GLI1 [KO:K16797]
107501918  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
107502145  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X2 [KO:K04678] [EC:2.3.2.26]
107502401  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
107502583  MEGF8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
107502872  GAS1; growth arrest-specific protein 1 [KO:K06232]
107503391  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107503771  GRK2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
107503915  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
107504039  CSNK1D; casein kinase I isoform X2 [KO:K08959] [EC:2.7.11.1]
107508514  EFCAB7; EF-hand calcium-binding domain-containing protein 7 isoform X1 [KO:K23852]
107508982  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
107509496  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
107511023  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
107511590  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107512153  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
107512750  GPR161; G-protein coupled receptor 161 isoform X2 [KO:K08439]
107512804  SMO; smoothened homolog [KO:K06226]
107513450  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
107513552  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
107513710  BOC; brother of CDO isoform X1 [KO:K20020]
107514148  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
107514238  DHH; desert hedgehog protein [KO:K11990]
107515574  SUFU; suppressor of fused homolog isoform X2 [KO:K06229]
107515826  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
107516080  MOSMO; modulator of smoothened protein [KO:K23663]
107516788  IHH; indian hedgehog protein [KO:K11989]
107517498  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
107517587  [KO:K10523]
107517620  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107518086  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
107518868  SHH; sonic hedgehog protein isoform X3 [KO:K11988]
107519010  EVC2; limbin isoform X1 [KO:K19608]
107519024  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
107519169  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
107519258  [KO:K08960] [EC:2.7.11.1]
107519437  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107520007  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
107520348  [KO:K06231]
107520839  DISP1; protein dispatched homolog 1 isoform X1 [KO:K24680]
107520878  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
107521021  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
107521431  IQCE; LOW QUALITY PROTEIN: IQ domain-containing protein E [KO:K24677]
107521681  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
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
ray04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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