KEGG   PATHWAY: rro04340
Entry
rro04340                    Pathway                                
Name
Hedgehog signaling pathway - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro04340  Hedgehog signaling pathway
rro04340

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104653947  CDON; LOW QUALITY PROTEIN: cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
104654682  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X2 [KO:K10604] [EC:2.3.2.27]
104654988  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
104655037  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
104655921  CSNK1G1; casein kinase I isoform X2 [KO:K08958] [EC:2.7.11.1]
104656429  CUL3; cullin-3 isoform X1 [KO:K03869]
104656496  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
104656524  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
104658713  MEGF8; multiple epidermal growth factor-like domains protein 8 isoform X2 [KO:K23664]
104658979  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
104659833  KIF3A; kinesin-like protein KIF3A isoform X8 [KO:K10394]
104659844  SPOP; speckle-type POZ protein [KO:K10523]
104660042  IHH; indian hedgehog protein [KO:K11989]
104660621  BOC; brother of CDO isoform X2 [KO:K20020]
104661051  [KO:K04345] [EC:2.7.11.11]
104661933  DISP1; protein dispatched homolog 1 [KO:K24680]
104662061  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
104663095  ARRB2; beta-arrestin-2 isoform X4 [KO:K04439]
104663129  GLI3; transcriptional activator GLI3 [KO:K06230]
104664749  GRK2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
104664962  IQCE; IQ domain-containing protein E isoform X3 [KO:K24677]
104665104  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
104665596  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
104666156  SHH; LOW QUALITY PROTEIN: sonic hedgehog protein [KO:K11988]
104667014  CUL1; cullin-1 [KO:K03347]
104667565  EVC2; limbin isoform X1 [KO:K19608]
104667569  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
104668066  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
104668970  GPR161; G-protein coupled receptor 161 isoform X2 [KO:K08439]
104669119  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
104669226  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
104670124  FBXW11; F-box/WD repeat-containing protein 11 isoform X2 [KO:K03362]
104670950  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
104671446  CSNK1G2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
104671949  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
104672074  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
104672610  GLI2; zinc finger protein GLI2 [KO:K16798]
104674349  KIF7; kinesin-like protein KIF7 isoform X2 [KO:K18806]
104674447  SMO; smoothened homolog isoform X1 [KO:K06226]
104675498  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
104676714  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
104677168  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104677489  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104677933  CSNK1A1L; casein kinase I [KO:K08957] [EC:2.7.11.1]
104678257  PTCH2; protein patched homolog 2 [KO:K11101]
104679310  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
104679543  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678]
104679724  DHH; desert hedgehog protein [KO:K11990]
104680771  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
104680990  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
104682106  MOSMO; modulator of smoothened protein [KO:K23663]
104682248  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104682362  GLI1; zinc finger protein GLI1 [KO:K16797]
104682535  [KO:K08960] [EC:2.7.11.1]
115894030  GAS1; growth arrest-specific protein 1 [KO:K06232]
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
rro04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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