KEGG   PATHWAY: xtr04340
Entry
xtr04340                    Pathway                                
Name
Hedgehog signaling pathway - Xenopus tropicalis (tropical clawed frog)
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
xtr04340  Hedgehog signaling pathway
xtr04340

Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
100036603  dhh; desert hedgehog protein precursor [KO:K11990]
100038034  csnk1g3; casein kinase I [KO:K08958] [EC:2.7.11.1]
100038053  prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100038071  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
100038194  smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
100101741  arrb2; beta-arrestin-2 [KO:K04439]
100101789  gli3; transcriptional activator GLI3 isoform X1 [KO:K06230]
100124788  evc; ellis-van Creveld syndrome protein [KO:K19605]
100124946  kif7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
100144972  mosmo; uncharacterized protein C16orf52 homolog [KO:K23663]
100145111  ihh; indian hedgehog protein isoform X2 [KO:K11989]
100145686  kif3a; kinesin-like protein KIF3A isoform X2 [KO:K10394]
100170148  sufu; suppressor of fused homolog [KO:K06229]
100170613  gpr161; G-protein coupled receptor 161 [KO:K08439]
100379889  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
100485267  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
100486349  arrb1; beta-arrestin-1 isoform X2 [KO:K04439]
100487601  shh; sonic hedgehog protein [KO:K11988]
100488597  [KO:K04345] [EC:2.7.11.11]
100489648  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100489914  lrp2; low-density lipoprotein receptor-related protein 2 isoform X2 [KO:K06233]
100490766  hhat; protein-cysteine N-palmitoyltransferase HHAT isoform X2 [KO:K24678]
100491582  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100491644  smo; smoothened homolog [KO:K06226]
100492061  ptch1; protein patched homolog 1 isoform X1 [KO:K06225]
100492803  cdon; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
100492958  ptch2; protein patched homolog 2 [KO:K11101]
100494064  gli1; zinc finger protein GLI1 [KO:K16797]
100494373  iqce; IQ domain-containing protein E [KO:K24677]
100494954  efcab7; EF-hand calcium-binding domain-containing protein 7 isoform X2 [KO:K23852]
100495651  evc2; limbin [KO:K19608]
100496804  disp1; protein dispatched homolog 1 isoform X1 [KO:K24680]
100496850  megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
100497988  spopl; speckle-type POZ protein-like [KO:K10523]
100498653  gli2; zinc finger protein GLI2 [KO:K16798]
101731553  [KO:K04345] [EC:2.7.11.11]
105946713  [KO:K04345] [EC:2.7.11.11]
108648814  [KO:K04345] [EC:2.7.11.11]
116407821  [KO:K04345] [EC:2.7.11.11]
116407822  [KO:K04345] [EC:2.7.11.11]
116407825  [KO:K04345] [EC:2.7.11.11]
116411737  [KO:K04345] [EC:2.7.11.11]
394599  spop; speckle-type POZ protein [KO:K10523]
394689  csnk1d; casein kinase I isoform delta [KO:K08959] [EC:2.7.11.1]
407897  csnk1a1; casein kinase I [KO:K08957] [EC:2.7.11.1]
448045  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
448124  csnk1g1; casein kinase I [KO:K08958] [EC:2.7.11.1]
448466  hhip; hedgehog-interacting protein [KO:K06231]
493512  hhatl; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
496553  csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
548442  csnk1g2; casein kinase I [KO:K08958] [EC:2.7.11.1]
548729  cul3; cullin-3 [KO:K03869]
548862  ccndx; cyclin Dx [KO:K04503]
549140  btrc; F-box/WD repeat-containing protein 1A [KO:K03362]
549157  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
549665  mgrn1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
734121  cul1; cullin-1 [KO:K03347]
779957  scube2; signal peptide, CUB and EGF-like domain-containing protein 2 precursor [KO:K24706]
780149  gas1; growth arrest-specific protein 1 precursor [KO:K06232]
780199  boc; brother of CDO precursor [KO:K20020]
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
xtr04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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