KEGG   PATHWAY: rno04340
Entry
rno04340                    Pathway                                

Name
Hedgehog signaling pathway - Rattus norvegicus (rat)
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
rno04340  Hedgehog signaling pathway
rno04340

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
89830  Ptch1; patched 1 [KO:K06225]
25273  Smo; smoothened, frizzled class receptor [KO:K06226]
289180  Gpr161; G protein-coupled receptor 161 [KO:K08439]
25636  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
113927  Csnk1a1; casein kinase 1, alpha 1 [KO:K08957] [EC:2.7.11.1]
64086  Csnk1g1; casein kinase 1, gamma 1 [KO:K08958] [EC:2.7.11.1]
64823  Csnk1g3; casein kinase 1, gamma 3 [KO:K08958] [EC:2.7.11.1]
65278  Csnk1g2; casein kinase 1, gamma 2 [KO:K08958] [EC:2.7.11.1]
64462  Csnk1d; casein kinase 1, delta [KO:K08959] [EC:2.7.11.1]
58822  Csnk1e; casein kinase 1, epsilon [KO:K08960] [EC:2.7.11.1]
84027  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
140589  Gli1; GLI family zinc finger 1 [KO:K16797]
304729  Gli2; GLI family zinc finger 2 [KO:K16798]
140588  Gli3; GLI family zinc finger 3 [KO:K06230]
361769  Sufu; SUFU negative regulator of hedgehog signaling [KO:K06229]
293047  Kif7; kinesin family member 7 [KO:K18806]
291936  Hhip; Hedgehog-interacting protein [KO:K06231]
58919  Ccnd1; cyclin D1 [KO:K04503]
64033  Ccnd2; cyclin D2 [KO:K10151]
24224  Bcl2; BCL2, apoptosis regulator [KO:K02161]
362356  Cul1; cullin 1 [KO:K03347]
303024  Fbxw11; F-box and WD repeat domain containing 11 [KO:K03362]
361765  Btrc; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
29499  Shh; sonic hedgehog [KO:K11988]
84399  Ihh; Indian hedgehog [KO:K11989]
84380  Dhh; desert hedgehog [KO:K11990]
360715  Boc; BOC cell adhesion associated, oncogene regulated [KO:K20020]
50938  Cdon; cell adhesion associated, oncogene regulated [KO:K20033]
683470  Gas1; growth arrest-specific 1 [KO:K06232]
29216  Lrp2; LDL receptor related protein 2 [KO:K06233]
102547219  uncharacterized LOC102547219 [KO:K23663]
114029  Megf8; multiple EGF-like-domains 8 [KO:K23664]
302938  Mgrn1; mahogunin ring finger 1 [KO:K10604] [EC:2.3.2.27]
303614  Smurf2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
690516  Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
25238  Grk2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
25372  Grk3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
289712  Evc; EvC ciliary complex subunit 1 [KO:K19605]
289711  Evc2; EvC ciliary complex subunit 2 [KO:K19608]
25387  Arrb1; arrestin, beta 1 [KO:K04439]
25388  Arrb2; arrestin, beta 2 [KO:K04439]
84392  Kif3a; kinesin family member 3a [KO:K10394]
301555  Cul3; cullin 3 [KO:K03869]
287643  Spop; speckle type BTB/POZ protein [KO:K10523]
296532  Spopl; speckle type BTB/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
rno04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

DBGET integrated database retrieval system