KEGG   PATHWAY: fpg04340
Entry
fpg04340                    Pathway                                
Name
Hedgehog signaling pathway - Falco peregrinus (peregrine falcon)
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
fpg04340  Hedgehog signaling pathway
fpg04340

Organism
Falco peregrinus (peregrine falcon) [GN:fpg]
Gene
101910491  EVC; EvC ciliary complex subunit 1 [KO:K19605]
101910663  EVC2; EvC ciliary complex subunit 2 [KO:K19608]
101911159  CUL1; cullin 1 [KO:K03347]
101911274  SPOP; speckle type BTB/POZ protein [KO:K10523]
101911546  [KO:K23663]
101911656  GRK2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
101912554  SHH; sonic hedgehog [KO:K11988]
101913718  LRP2; LDL receptor related protein 2 [KO:K06233]
101914153  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
101914298  [KO:K08959] [EC:2.7.11.1]
101914395  GLI1; GLI family zinc finger 1 [KO:K16797]
101914457  PTCH2; patched 2 [KO:K11101]
101914564  GLI3; GLI family zinc finger 3 [KO:K06230]
101914830  CSNK1G3; casein kinase 1 gamma 3 [KO:K08958] [EC:2.7.11.1]
101914937  CCND1; cyclin D1 [KO:K04503]
101915344  PTCH1; patched 1 [KO:K06225]
101915784  KIF7; kinesin family member 7 [KO:K18806]
101916319  DISP1; dispatched RND transporter family member 1 [KO:K24680]
101916842  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
101917004  SPOPL; speckle type BTB/POZ protein like [KO:K10523]
101917082  IQCE; IQ motif containing E [KO:K24677]
101917869  CSNK1G2; casein kinase 1 gamma 2 [KO:K08958] [EC:2.7.11.1]
101918488  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
101919085  HHAT; hedgehog acyltransferase [KO:K24678]
101919127  CSNK1E; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
101919573  ARRB1; arrestin beta 1 [KO:K04439]
101920205  HHIP; hedgehog interacting protein [KO:K06231]
101920354  CCND2; cyclin D2 [KO:K10151]
101920502  GLI2; GLI family zinc finger 2 [KO:K16798]
101920782  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
101921077  KIF3A; kinesin family member 3A [KO:K10394]
101921145  CUL3; cullin 3 [KO:K03869]
101921728  BCL2; BCL2, apoptosis regulator [KO:K02161]
101921803  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101921899  IHH; indian hedgehog [KO:K11989]
101921904  SMO; smoothened, frizzled class receptor [KO:K06226]
101922747  MGRN1; mahogunin ring finger 1 [KO:K10604] [EC:2.3.2.27]
101923309  EFCAB7; EF-hand calcium binding domain 7 [KO:K23852]
101923337  SCUBE2; signal peptide, CUB domain and EGF like domain containing 2 [KO:K24706]
101923555  HHATL; hedgehog acyltransferase-like [KO:K24679]
101923866  CSNK1G1; casein kinase 1 gamma 1 [KO:K08958] [EC:2.7.11.1]
101924206  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
101924223  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
101924263  BOC; BOC cell adhesion associated, oncogene regulated [KO:K20020]
101924309  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
101924458  SUFU; SUFU negative regulator of hedgehog signaling [KO:K06229]
101924476  CDON; cell adhesion associated, oncogene regulated [KO:K20033]
101924775  [KO:K08439]
101924939  GPR161; G-protein coupled receptor 161 [KO:K08439]
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
fpg04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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