KEGG   PATHWAY: snh04340
Entry
snh04340                    Pathway                                
Name
Hedgehog signaling pathway - Salvelinus namaycush (lake trout)
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
snh04340  Hedgehog signaling pathway
snh04340

Organism
Salvelinus namaycush (lake trout) [GN:snh]
Gene
120044320  ptch1; protein patched homolog 1 [KO:K06225]
120062919  protein patched homolog 1-like [KO:K06225]
120020082  protein patched homolog 1-like [KO:K11101]
120055874  protein patched homolog 1 [KO:K11101]
120031810  smoothened homolog [KO:K06226]
120032283  smoothened homolog [KO:K06226]
120064325  gpr161a; G-protein coupled receptor 161 isoform X1 [KO:K08439]
120019042  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
120020291  cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
120039714  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120033914  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
120055956  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
120054595  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
120048228  casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
120062544  casein kinase I-like isoform X1 [KO:K08957] [EC:2.7.11.1]
120020745  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
120041352  casein kinase I-like [KO:K08958] [EC:2.7.11.1]
120035643  casein kinase I [KO:K08958] [EC:2.7.11.1]
120052491  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
120054039  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
120066388  casein kinase I-like isoform X1 [KO:K08958] [EC:2.7.11.1]
120054828  csnk1g2b; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
120042708  casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120042781  casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120046802  casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120029559  casein kinase I-like isoform X1 [KO:K08959] [EC:2.7.11.1]
120033923  casein kinase I-like [KO:K08960] [EC:2.7.11.1]
120045709  casein kinase I-like [KO:K08960] [EC:2.7.11.1]
120037868  casein kinase I [KO:K08960] [EC:2.7.11.1]
120029827  casein kinase I-like [KO:K08960] [EC:2.7.11.1]
120033312  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120051240  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
120064165  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
120058450  glycogen synthase kinase-3 beta-like isoform X1 [KO:K03083] [EC:2.7.11.26]
120020218  zinc finger protein GLI1-like [KO:K16797]
120065568  gli1; LOW QUALITY PROTEIN: zinc finger protein GLI1 [KO:K16797]
120033190  zinc finger protein GLI2-like [KO:K16798]
120050733  zinc finger protein GLI2-like [KO:K16798]
120063931  zinc finger protein GLI2-like [KO:K16798]
120058320  gli2a; zinc finger protein GLI2a [KO:K16798]
120027865  transcriptional activator GLI3-like [KO:K06230]
120051119  transcriptional activator GLI3-like [KO:K06230]
120017501  suppressor of fused homolog isoform X1 [KO:K06229]
120046444  suppressor of fused homolog isoform X1 [KO:K06229]
120025246  kinesin-like protein kif7 [KO:K18806]
120047664  kinesin-like protein kif7 [KO:K18806]
120034941  hedgehog-interacting protein-like [KO:K06231]
120035175  hedgehog-interacting protein-like [KO:K06231]
120025309  G1/S-specific cyclin-D1-like [KO:K04503]
120045999  G1/S-specific cyclin-D1 [KO:K04503]
120054165  G1/S-specific cyclin-D1-like [KO:K04503]
120066776  G1/S-specific cyclin-D1-like [KO:K04503]
120042003  G1/S-specific cyclin-D2-like [KO:K10151]
120032172  G1/S-specific cyclin-D2-like [KO:K10151]
120044064  G1/S-specific cyclin-D2-like [KO:K10151]
120034023  G1/S-specific cyclin-D2-like [KO:K10151]
120049937  G1/S-specific cyclin-D2-like [KO:K10151]
120053511  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
120019795  apoptosis regulator Bcl-2-like [KO:K02161]
120027961  apoptosis regulator Bcl-2-like [KO:K02161]
120055940  apoptosis regulator Bcl-2-like [KO:K02161]
120051010  apoptosis regulator Bcl-2-like [KO:K02161]
120020331  cullin-1 [KO:K03347]
120027736  cullin-1-like isoform X1 [KO:K03347]
120055897  cullin-1-like [KO:K03347]
120048172  F-box/WD repeat-containing protein 11-like [KO:K03362]
120045059  F-box/WD repeat-containing protein 11-like [KO:K03362]
120062303  F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
120057210  F-box/WD repeat-containing protein 11-like isoform X1 [KO:K03362]
120046626  hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678] [EC:2.3.1.-]
120055688  hhatla; hedgehog acyltransferase like, a isoform X1 [KO:K24679]
120019836  tiggy-winkle hedgehog protein-like [KO:K11988]
120028069  sonic hedgehog protein A-like [KO:K11988]
120050426  sonic hedgehog protein A-like [KO:K11988]
120055265  tiggy-winkle hedgehog protein-like [KO:K11988]
120035282  indian hedgehog B protein-like [KO:K11989]
120036505  indian hedgehog B protein-like [KO:K11989]
120051514  indian hedgehog B protein-like [KO:K11989]
120058824  indian hedgehog protein-like [KO:K11990]
120061020  desert hedgehog protein A-like [KO:K11990]
120019016  protein dispatched homolog 1-like [KO:K24680]
120024094  protein dispatched homolog 1-like isoform X1 [KO:K24680]
120025276  signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
120052781  signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
120027703  brother of CDO-like [KO:K20020]
120050969  brother of CDO-like [KO:K20020]
120025837  growth arrest-specific protein 1-like [KO:K06232]
120044937  growth arrest-specific protein 1-like [KO:K06232]
120035691  gas1a; growth arrest-specific protein 1a [KO:K06232]
120025118  growth arrest-specific protein 1-like [KO:K06232]
120048135  growth arrest-specific protein 1-like [KO:K06232]
120045804  lrp2b; low-density lipoprotein receptor-related protein 2 [KO:K06233]
120057774  low-density lipoprotein receptor-related protein 2-like [KO:K06233]
120064011  lrp2a; low-density lipoprotein receptor-related protein 2a [KO:K06233]
120030098  uncharacterized protein C16orf52 homolog B-like [KO:K23663]
120040634  uncharacterized protein C16orf52 homolog B [KO:K23663]
120040635  uncharacterized protein C16orf52 homolog B [KO:K23663]
120045726  uncharacterized protein C16orf52 homolog B-like isoform X1 [KO:K23663]
120048659  multiple epidermal growth factor-like domains protein 8 [KO:K23664]
120048780  megf8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
120044555  probable E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
120034098  probable E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
120039033  E3 ubiquitin-protein ligase SMURF2-like [KO:K04678] [EC:2.3.2.26]
120032501  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
120034150  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
120065829  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
120020946  beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
120026183  beta-adrenergic receptor kinase 2-like [KO:K00910] [EC:2.7.11.15]
120021923  ellis-van Creveld syndrome protein [KO:K19605]
120064110  limbin-like [KO:K19608]
120054566  efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
120041420  IQ domain-containing protein E-like [KO:K24677]
120042372  IQ domain-containing protein E-like [KO:K24677]
120030609  arrestin red cell-like [KO:K04439]
120045158  arrestin red cell isoform X1 [KO:K04439]
120037048  arrb1; beta-arrestin-1 [KO:K04439]
120049801  arrb2b; arrestin, beta 2b [KO:K04439]
120057103  arrestin red cell [KO:K04439]
120047914  kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
120018436  cullin-3 [KO:K03869]
120020115  cullin-3-like [KO:K03869]
120028634  cullin-3 [KO:K03869]
120056174  cullin-3-like [KO:K03869]
120040733  speckle-type POZ protein [KO:K10523]
120034238  speckle-type POZ protein-like [KO:K10523]
120046377  speckle-type POZ protein-like [KO:K10523]
120064502  speckle-type POZ protein-like A [KO:K10523]
120058538  speckle-type POZ protein-like A [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
snh04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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