KEGG   PATHWAY: pvp04340
Entry
pvp04340                    Pathway                                
Name
Hedgehog signaling pathway - Pteropus vampyrus (large flying fox)
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
pvp04340  Hedgehog signaling pathway
pvp04340

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288320  [KO:K08960] [EC:2.7.11.1]
105288332  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105290238  SMO; smoothened homolog [KO:K06226]
105290318  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
105290875  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
105291048  IHH; indian hedgehog protein [KO:K11989]
105291589  HHIP; hedgehog-interacting protein [KO:K06231]
105291748  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
105292033  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
105292717  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
105293261  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105293529  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
105293551  KIF3A; kinesin-like protein KIF3A isoform X3 [KO:K10394]
105294244  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
105294458  GLI2; zinc finger protein GLI2 [KO:K16798]
105294598  IQCE; IQ domain-containing protein E [KO:K24677]
105294751  CUL3; cullin-3 isoform X1 [KO:K03869]
105295417  SPOP; speckle-type POZ protein [KO:K10523]
105295712  CUL1; cullin-1 isoform X1 [KO:K03347]
105296806  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X2 [KO:K20033]
105297117  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
105297535  DHH; desert hedgehog protein [KO:K11990]
105297636  ARRB1; beta-arrestin-1 isoform X2 [KO:K04439]
105297710  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
105298355  EFCAB7; EF-hand calcium-binding domain-containing protein 7 isoform X2 [KO:K23852]
105298927  SHH; LOW QUALITY PROTEIN: sonic hedgehog protein [KO:K11988]
105299298  FBXW11; F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
105299427  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
105300308  HHAT; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678]
105300409  CSNK1G2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
105301125  CSNK1D; casein kinase I isoform X2 [KO:K08959] [EC:2.7.11.1]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301497  GPR161; G-protein coupled receptor 161 isoform X1 [KO:K08439]
105301698  DISP1; protein dispatched homolog 1 [KO:K24680]
105301826  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
105301836  EVC; ellis-van Creveld syndrome protein [KO:K19605]
105301837  EVC2; limbin isoform X1 [KO:K19608]
105303083  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
105303216  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
105304642  BTRC; F-box/WD repeat-containing protein 1A isoform X3 [KO:K03362]
105305018  BOC; brother of CDO [KO:K20020]
105305149  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
105305205  KIF7; kinesin-like protein KIF7 [KO:K18806]
105306062  CUNH16orf52; uncharacterized protein C16orf52 homolog [KO:K23663]
105306915  PTCH1; protein patched homolog 1 isoform X3 [KO:K06225]
105307128  [KO:K04503]
105307363  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
105307376  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
105308265  GAS1; LOW QUALITY PROTEIN: growth arrest-specific protein 1 [KO:K06232]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105309657  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
105309917  GRK2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
105310465  [KO:K08959] [EC:2.7.11.1]
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
pvp04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

DBGET integrated database retrieval system