KEGG   PATHWAY: pgig04340
Entry
pgig04340                   Pathway                                
Name
Hedgehog signaling pathway - Pteropus giganteus (Indian 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
pgig04340  Hedgehog signaling pathway
pgig04340

Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120616899  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
120619682  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
120600969  SMO; smoothened homolog [KO:K06226]
120617691  GPR161; G-protein coupled receptor 161 isoform X1 [KO:K08439]
120583269  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120618485  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
120581532  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
120590889  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
120613159  casein kinase I [KO:K08958] [EC:2.7.11.1]
120604535  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
120583718  CSNK1G2; LOW QUALITY PROTEIN: casein kinase I [KO:K08958] [EC:2.7.11.1]
120600129  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120614818  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
120586669  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120604955  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
120606282  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
120591678  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
120609147  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
120599389  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
120613331  hedgehog-interacting protein [KO:K06231]
120584714  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120607308  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
120584396  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
120601485  CUL1; cullin-1 [KO:K03347]
120614879  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
120609176  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
120608497  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
120582219  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
120582128  SHH; sonic hedgehog protein [KO:K11988]
120587672  IHH; indian hedgehog protein isoform X1 [KO:K11989]
120618202  DHH; desert hedgehog protein [KO:K11990]
120619215  DISP1; protein dispatched homolog 1 isoform X1 [KO:K24680]
120603172  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
120586631  BOC; brother of CDO isoform X1 [KO:K20020]
120610449  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
120612930  GAS1; growth arrest-specific protein 1 [KO:K06232]
120597126  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
120584554  MOSMO; modulator of smoothened protein isoform X1 [KO:K23663]
120592377  MEGF8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
120620347  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
120616538  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
120600365  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
120601990  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
120584771  GRK2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
120582859  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
120582858  EVC2; LOW QUALITY PROTEIN: limbin [KO:K19608]
120622187  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
120613722  IQCE; IQ domain-containing protein E [KO:K24677]
120607869  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
120590357  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
120616513  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
120597077  CUL3; cullin-3 isoform X1 [KO:K03869]
120588931  speckle-type POZ protein [KO:K10523]
120611953  SPOPL; speckle-type POZ protein-like isoform X1 [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
pgig04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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