KEGG   PATHWAY: rtp04340
Entry
rtp04340                    Pathway                                
Name
Hedgehog signaling pathway - Rhincodon typus (whale shark)
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
rtp04340  Hedgehog signaling pathway
rtp04340

Organism
Rhincodon typus (whale shark) [GN:rtp]
Gene
109910728  ptch1; protein patched homolog 1 [KO:K06225]
109919118  ptch2; protein patched homolog 1 [KO:K11101]
109931227  smo; smoothened homolog [KO:K06226]
109920314  gpr161a; G-protein coupled receptor 161 isoform X1 [KO:K08439]
109919525  G-protein coupled receptor 161-like [KO:K08439]
109910402  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
109937447  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
109918708  csnk1a1; casein kinase I isoform X2 [KO:K08957] [EC:2.7.11.1]
109912502  casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
109934754  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
109913713  casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
109935778  casein kinase I [KO:K08960] [EC:2.7.11.1]
109910841  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
109923305  transcriptional activator GLI3-like isoform X2 [KO:K06230]
109911580  sufu; suppressor of fused homolog [KO:K06229]
109927090  kif7; kinesin-like protein kif7 [KO:K18806]
109913138  hedgehog-interacting protein [KO:K06231]
109919627  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109925537  G1/S-specific cyclin-D1-like [KO:K04503]
109931888  G1/S-specific cyclin-D2-like [KO:K10151]
109930204  apoptosis regulator Bcl-2-like isoform X2 [KO:K02161]
109916300  cul1b; cullin-1b [KO:K03347]
109915133  F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
109920037  beta-TrCP isoform X1 [KO:K03362]
109918648  hhatla; hedgehog acyltransferase like, a [KO:K24679]
109923465  shha; sonic hedgehog protein A [KO:K11988]
109915863  indian hedgehog protein [KO:K11989]
109912548  cdon; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
109919271  growth arrest-specific protein 1-like [KO:K06232]
109914792  growth arrest-specific protein 1-like isoform X1 [KO:K06232]
109917117  low-density lipoprotein receptor-related protein 2-like [KO:K06233]
109913757  E3 ubiquitin-protein ligase MGRN1-like isoform X1 [KO:K10604] [EC:2.3.2.27]
109934829  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109914938  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
109927406  limbin isoform X1 [KO:K19608]
109913604  S-arrestin-like [KO:K04439]
109916453  arrb1; beta-arrestin-1 [KO:K04439]
109925864  arrestin red cell isoform X1 [KO:K04439]
109927707  kif3a; kinesin-like protein KIF3A [KO:K10394]
109918076  cullin-3 [KO:K03869]
109929183  speckle-type POZ protein [KO:K10523]
109936812  spopla; speckle-type POZ protein-like A [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
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
rtp04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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