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
102547219  Mosmo; modulator of smoothened protein [KO:K23663]
113927  Csnk1a1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
114029  Megf8; multiple epidermal growth factor-like domains protein 8 precursor [KO:K23664]
140588  Gli3; transcriptional activator GLI3 [KO:K06230]
140589  Gli1; zinc finger protein GLI1 [KO:K16797]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
25238  Grk2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
25273  Smo; protein smoothened precursor [KO:K06226]
25372  Grk3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
25387  Arrb1; beta-arrestin-1 [KO:K04439]
25388  Arrb2; beta-arrestin-2 [KO:K04439]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
287643  Spop; speckle-type POZ protein [KO:K10523]
289180  Gpr161; G-protein coupled receptor 161 [KO:K08439]
289338  Disp1; protein dispatched homolog 1 [KO:K24680]
289344  Hhat; protein-cysteine N-palmitoyltransferase HHAT precursor [KO:K24678]
289711  Evc2; limbin [KO:K19608]
289712  Evc; evC complex member EVC [KO:K19605]
291936  Hhip; hedgehog-interacting protein precursor [KO:K06231]
29216  Lrp2; low-density lipoprotein receptor-related protein 2 precursor [KO:K06233]
293047  Kif7; kinesin-like protein KIF7 isoform X2 [KO:K18806]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
29499  Shh; sonic hedgehog protein precursor [KO:K11988]
296532  Spopl; speckle-type POZ protein-like [KO:K10523]
301073  Hhatl; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
301555  Cul3; cullin-3 [KO:K03869]
302938  Mgrn1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
303024  Fbxw11; F-box/WD repeat-containing protein 11 isoform 1 [KO:K03362]
303614  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
304318  Iqce; IQ domain-containing protein E isoform X2 [KO:K24677]
304729  Gli2; zinc finger protein GLI2 [KO:K16798]
360715  Boc; brother of CDO precursor [KO:K20020]
361765  Btrc; F-box/WD repeat-containing protein 1A [KO:K03362]
361769  Sufu; suppressor of fused homolog [KO:K06229]
362356  Cul1; cullin-1 [KO:K03347]
362549  Efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
499241  Scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
50938  Cdon; cell adhesion molecule-related/down-regulated by oncogenes precursor [KO:K20033]
58822  Csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
64033  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
64086  Csnk1g1; casein kinase I isoform gamma-1 [KO:K08958] [EC:2.7.11.1]
64462  Csnk1d; casein kinase I isoform delta isoform 1 [KO:K08959] [EC:2.7.11.1]
64823  Csnk1g3; casein kinase I isoform gamma-3 isoform 1 [KO:K08958] [EC:2.7.11.1]
65278  Csnk1g2; casein kinase I isoform gamma-2 isoform 1 [KO:K08958] [EC:2.7.11.1]
683470  Gas1; growth arrest-specific protein 1 [KO:K06232]
690516  Smurf1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84380  Dhh; desert hedgehog protein precursor [KO:K11990]
84392  Kif3a; kinesin-like protein KIF3A [KO:K10394]
84399  Ihh; indian hedgehog protein precursor [KO:K11989]
89830  Ptch1; protein patched homolog 1 isoform 2 [KO:K06225]
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
rno04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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