KEGG   PATHWAY: xco04340
Entry
xco04340                    Pathway                                

Name
Hedgehog signaling pathway - Xiphophorus couchianus (Monterrey platyfish)
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
xco04340  Hedgehog signaling pathway
xco04340

Organism
Xiphophorus couchianus (Monterrey platyfish) [GN:xco]
Gene
114154713  ptch1; protein patched homolog 1 [KO:K06225]
114146891  ptch2; protein patched homolog 2 [KO:K11101]
114160844  smo; smoothened homolog [KO:K06226]
114148522  gpr161; G-protein coupled receptor 161 [KO:K08439]
114150831  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114144649  prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114146401  cAMP-dependent protein kinase catalytic subunit beta-like isoform X1 [KO:K04345] [EC:2.7.11.11]
114159753  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114152643  csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
114150815  casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
114142834  csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
114146655  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
114147957  csnk1d; casein kinase I [KO:K08959] [EC:2.7.11.1]
114161839  casein kinase I-like [KO:K08960] [EC:2.7.11.1]
114159847  csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
114147695  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114135667  gli1; zinc finger protein GLI1 isoform X1 [KO:K16797]
114147937  gli2; zinc finger protein GLI2 isoform X1 [KO:K16798]
114140508  zinc finger protein GLI2-like [KO:K16798]
114136826  transcriptional activator GLI3-like isoform X1 [KO:K06230]
114138505  sufu; suppressor of fused homolog isoform X1 [KO:K06229]
114143615  kif7; kinesin-like protein KIF7 [KO:K18806]
114145203  hhip; hedgehog-interacting protein isoform X1 [KO:K06231]
114143123  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
114160373  G1/S-specific cyclin-D2-like [KO:K10151]
114152343  G1/S-specific cyclin-D2-like isoform X1 [KO:K10151]
114160881  G1/S-specific cyclin-D2-like [KO:K10151]
114146495  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
114136425  cul1; cullin-1 [KO:K03347]
114138794  F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
114136393  shh; sonic hedgehog protein [KO:K11988]
114148134  indian hedgehog B protein-like [KO:K11989]
114142553  dhh; desert hedgehog protein [KO:K11990]
114136683  boc; brother of CDO [KO:K20020]
114133260  cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
114143565  growth arrest-specific protein 1-like [KO:K06232]
114154894  growth arrest-specific protein 1-like [KO:K06232]
114150115  growth arrest-specific protein 1-like [KO:K06232]
114151668  low-density lipoprotein receptor-related protein 2-like [KO:K06233]
114148390  lrp2; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
114149015  low-density lipoprotein receptor-related protein 2-like [KO:K06233]
114159944  mosmo; modulator of smoothened protein [KO:K23663]
114142345  megf8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
114160056  mgrn1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
114159764  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
114159826  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
114144713  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
114150251  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
114135906  evc; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
114135756  evc2; limbin [KO:K19608]
114161734  beta-arrestin-1 [KO:K04439]
114153593  arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
114139220  kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
114146168  cullin-3-like [KO:K03869]
114133189  cullin-3 [KO:K03869]
114136829  spop; speckle-type POZ protein [KO:K10523]
114148871  spopl; speckle-type POZ protein-like [KO:K10523]
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
Related
pathway
xco04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
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