KEGG   PATHWAY: ko04340Help
Entry
ko04340                     Pathway                                

Name
Hedgehog signaling pathway
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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
ko04340  Hedgehog signaling pathway
ko04340

Ortholog table
Module
M00678  Hedgehog signaling [PATH:ko04340]
Disease
H00263  Acrocallosal syndrome
H00267  Holoprosencephaly (HPE)
H00482  Brachydactyly
H00502  Pallister-Hall syndrome
H00503  Ellis-van Creveld syndrome
H00530  Joubert syndrome
H00607  46,XY disorders of sex development (Disorders of gonadal development)
H00646  Odontoonychodermal dysplasia
H00652  Solitary median maxillary central incisor syndrome
H00675  Acrocapitofemoral dysplasia
H00855  Triphalangeal thumb-polysyndactyly syndrome
H00886  Donnai-Barrow syndrome
H00895  Basal cell nevus syndrome
H01027  Anophthalmia and microphthalmia (A/M)
H01160  Schizencephaly
H01226  Polysyndactyly
H01667  Medulloblastoma
H02158  Weyers acrodental dysostosis
Orthology
K06225  patched 1
K11101  patched 2
K06226  smoothened
K08439  G protein-coupled receptor 161
K04345  protein kinase A [EC:2.7.11.11]
K08957  casein kinase 1, alpha [EC:2.7.11.1]
K08958  casein kinase 1, gamma [EC:2.7.11.1]
K08959  casein kinase 1, delta [EC:2.7.11.1]
K08960  casein kinase 1, epsilon [EC:2.7.11.1]
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K16797  zinc finger protein GLI1
K16798  zinc finger protein GLI2
K06230  zinc finger protein GLI3
K06229  suppressor of fused
K18806  kinesin family member 7
K06231  hedgehog interacting protein
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K02161  apoptosis regulator Bcl-2
K03347  cullin 1
K03362  F-box and WD-40 domain protein 1/11
K11988  sonic hedgehog
K11989  indian hedgehog
K11990  desert hedgehog
K20020  brother of CDO
K20033  cell adhesion molecule-related/down-regulated by oncogenes
K06232  growth arrest-specific 1
K06233  low density lipoprotein-related protein 2
K04678  E3 ubiquitin ligase SMURF1/2 [EC:2.3.2.26]
K00910  beta-adrenergic-receptor kinase [EC:2.7.11.15]
K19605  ellis van creveld syndrome protein 1
K19608  ellis van creveld syndrome protein 2
K04439  beta-arrestin
K10394  kinesin family member 3A
K03869  cullin 3
K10523  speckle-type POZ protein
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
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