KEGG   PATHWAY: xla04340
Entry
xla04340                    Pathway                                
Name
Hedgehog signaling pathway - Xenopus laevis (African 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
xla04340  Hedgehog signaling pathway
xla04340

Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
398215  ptch1.S; patched 1 S homeolog [KO:K06225]
108714691  ptch1.L; protein patched homolog 1 isoform X1 [KO:K06225]
397836  ptch2.S; patched 2 S homeolog [KO:K11101]
100191013  ptch2.L; patched 2 L homeolog [KO:K11101]
398216  smo.S; smoothened, frizzled class receptor S homeolog [KO:K06226]
100190780  smo.L; smoothened, frizzled class receptor L homeolog precursor [KO:K06226]
108697265  G-protein coupled receptor 161 [KO:K08439]
380388  prkacb.S; protein kinase cAMP-activated catalytic subunit beta S homeolog [KO:K04345] [EC:2.7.11.11]
100101276  prkaca.S; protein kinase, cAMP-dependent, alpha catalytic subunit S homeolog [KO:K04345] [EC:2.7.11.11]
108714187  prkacb.L; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108711677  prkaca.L; protein kinase, cAMP-dependent, alpha catalytic subunit L homeolog [KO:K04345] [EC:2.7.11.11]
379624  csnk1a1.L; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
380238  csnk1a1.S; casein kinase 1 alpha 1 S homeolog [KO:K08957] [EC:2.7.11.1]
431882  csnk1g1.S; casein kinase I isoform gamma-1 [KO:K08958] [EC:2.7.11.1]
444447  csnk1g2.L; casein kinase 1 gamma 2 L homeolog [KO:K08958] [EC:2.7.11.1]
100036840  csnk1g3.L; casein kinase 1 gamma 3 L homeolog [KO:K08958] [EC:2.7.11.1]
734338  csnk1g3.S; uncharacterized protein LOC734338 [KO:K08958] [EC:2.7.11.1]
108711327  csnk1g1.L; casein kinase I-like isoform X2 [KO:K08958] [EC:2.7.11.1]
380361  csnk1d.S; casein kinase I isoform delta [KO:K08959] [EC:2.7.11.1]
108701007  csnk1d.L; casein kinase I-like isoform X1 [KO:K08959] [EC:2.7.11.1]
399381  tptep2-csnk1e.L; TPTEP2-CSNK1E readthrough L homeolog [KO:K08960] [EC:2.7.11.1]
108715790  tptep2-csnk1e.S; casein kinase I [KO:K08960] [EC:2.7.11.1]
399097  gsk3b.L; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
779056  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
108708587  gli1.L; zinc finger protein GLI1-like isoform X1 [KO:K16797]
398350  gli1.S; zinc finger protein GLI1 isoform X1 [KO:K16797]
398107  gli2.S; GLI family zinc finger 2 S homeolog [KO:K16798]
397838  gli2.L; zinc finger protein GLI4 [KO:K16798]
397837  gli3.L; zinc finger protein GLI3 [KO:K06230]
108720004  gli3.S; zinc finger protein GLI3-like isoform X1 [KO:K06230]
444442  sufu.L; SUFU negative regulator of hedgehog signaling L homeolog [KO:K06229]
108697422  sufu.S; suppressor of fused homolog isoform X1 [KO:K06229]
108711454  kif7.L; kinesin-like protein KIF7 isoform X1 [KO:K18806]
380097  hhip.L; hedgehog interacting protein L homeolog precursor [KO:K06231]
108706669  hhip.S; hedgehog-interacting protein isoform X2 [KO:K06231]
379161  ccnd1.S; G1/S-specific cyclin-D1 b [KO:K04503]
379937  ccnd1.L; G1/S-specific cyclin-D1 [KO:K04503]
447748  ccndx.L; G1/S-specific cyclin-D1 [KO:K04503]
447541  MGC83948 protein [KO:K04503]
734882  ccnd2.S; cyclin D2 S homeolog [KO:K10151]
373667  ccnd2.L; G1/S-specific cyclin-D2 [KO:K10151]
100271914  bcl2.S; B-cell CLL/lymphoma 2 S homeolog [KO:K02161]
108719105  bcl2.L; apoptosis regulator Bcl-2 [KO:K02161]
734414  cul1.S; cullin 1 S homeolog [KO:K03347]
734526  cul1.L; uncharacterized protein LOC734526 [KO:K03347]
394362  btrc.S; beta-TrCP [KO:K03362]
397988  btrc.L; beta-TrCP-like isoform X1 [KO:K03362]
108716437  hhat.L; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
379179  hhatl.S; hedgehog acyltransferase like S homeolog [KO:K24679]
108718700  hhatl.L; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
398047  shh.L; sonic hedgehog protein precursor [KO:K11988]
108719826  shh.S; sonic hedgehog protein-like isoform X1 [KO:K11988]
378540  ihh.S; indian hedgehog protein precursor [KO:K11989]
108701295  ihh.L; indian hedgehog protein-like isoform X1 [KO:K11989]
378538  dhh.L; desert hedgehog protein A precursor [KO:K11990]
378539  dhh.S; desert hedgehog protein B precursor [KO:K11990]
108717699  disp1.S; protein dispatched homolog 1 isoform X1 [KO:K24680]
108716474  disp1.L; protein dispatched homolog 1 isoform X1 [KO:K24680]
100381032  scube2.L; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X2 [KO:K24706]
108715299  scube2.S; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X2 [KO:K24706]
443556  boc.L; BOC cell adhesion associated, oncogene regulated L homeolog precursor [KO:K20020]
108709290  boc.S; brother of CDO isoform X1 [KO:K20020]
108697576  cdon.S; cell adhesion molecule-related/down-regulated by oncogenes-like isoform X1 [KO:K20033]
373711  cdon.L; cell adhesion molecule-related/down-regulated by oncogenes precursor [KO:K20033]
108706992  gas1.S; growth arrest-specific protein 1 [KO:K06232]
108714684  gas1.L; growth arrest-specific protein 1 [KO:K06232]
100126618  lrp2.L; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
379458  mosmo.L; uncharacterized protein C16orf52 homolog B [KO:K23663]
443762  mosmo.S; uncharacterized protein C16orf52 homolog A [KO:K23663]
108697768  megf8.S; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
108696705  megf8.L; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
398990  mgrn1.S; mahogunin ring finger 1, E3 ubiquitin protein ligase S homeolog [KO:K10604] [EC:2.3.2.27]
398131  smurf1.L; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
398372  smurf2.S; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
108701209  E3 ubiquitin-protein ligase SMURF2-like isoform X2 [KO:K04678] [EC:2.3.2.26]
108703087  smurf1.S; E3 ubiquitin-protein ligase SMURF1-like isoform X1 [KO:K04678] [EC:2.3.2.26]
108707086  beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
108715724  beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
108698025  evc.L; ellis-van Creveld syndrome protein [KO:K19605]
108698024  evc2.L; limbin [KO:K19608]
447043  efcab7.L; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
108701553  iqce.L; IQ domain-containing protein E [KO:K24677]
447732  arrb1.S; arrestin beta 1 S homeolog [KO:K04439]
446401  arrb2.S; arrestin beta 2 S homeolog [KO:K04439]
444007  arrb2.L; arrestin red cell [KO:K04439]
108705153  arrb1.L; beta-arrestin-1 isoform X1 [KO:K04439]
399401  kif3a.L; kinesin family member 3A L homeolog [KO:K10394]
108713264  kif3a.S; kinesin-like protein KIF3A isoform X4 [KO:K10394]
446487  cul3.L; cullin-3-A [KO:K03869]
444103  cul3.S; cullin-3-B [KO:K03869]
379868  spop.L; speckle-type POZ protein A [KO:K10523]
779391  spop.S; speckle-type POZ protein B [KO:K10523]
443784  spopl.L; speckle-type POZ protein-like [KO:K10523]
108702947  spopl.S; speckle-type POZ protein-like [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
xla04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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