KEGG   PATHWAY: ccan04340
Entry
ccan04340                   Pathway                                
Name
Hedgehog signaling pathway - Castor canadensis (American beaver)
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
ccan04340  Hedgehog signaling pathway
ccan04340

Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109683424  Ptch1; protein patched homolog 1 [KO:K06225]
109698893  Ptch2; protein patched homolog 2 [KO:K11101]
109684128  Smo; smoothened homolog isoform X1 [KO:K06226]
109696041  Gpr161; G-protein coupled receptor 161 [KO:K08439]
109702294  G-protein coupled receptor 161-like [KO:K08439]
109688706  cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
109681298  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109688701  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109690568  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
109702106  LOW QUALITY PROTEIN: casein kinase I-like [KO:K08957] [EC:2.7.11.1]
109702984  casein kinase I-like isoform X1 [KO:K08957] [EC:2.7.11.1]
109693042  Csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
109694400  Csnk1g3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
109698863  Csnk1g2; casein kinase I [KO:K08958] [EC:2.7.11.1]
109703071  Csnk1d; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
109692849  casein kinase I [KO:K08960] [EC:2.7.11.1]
109685333  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
109686379  Gli1; zinc finger protein GLI1 isoform X1 [KO:K16797]
109693799  Gli2; zinc finger protein GLI2 [KO:K16798]
109676337  Gli3; transcriptional activator GLI3 isoform X1 [KO:K06230]
109691296  Sufu; suppressor of fused homolog isoform X1 [KO:K06229]
109687545  Kif7; LOW QUALITY PROTEIN: kinesin-like protein KIF7 [KO:K18806]
109680504  Hhip; hedgehog-interacting protein [KO:K06231]
109696351  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109688460  G1/S-specific cyclin-D2-like [KO:K10151]
109688461  G1/S-specific cyclin-D2 [KO:K10151]
109693757  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
109695511  Cul1; cullin-1 [KO:K03347]
109696980  Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
109691321  Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
109679353  Hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678] [EC:2.3.1.-]
109699452  Hhatl; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
109702047  Shh; sonic hedgehog protein [KO:K11988]
109691081  Ihh; indian hedgehog protein [KO:K11989]
109688932  desert hedgehog protein [KO:K11990]
109703084  desert hedgehog protein [KO:K11990]
109677861  Disp1; protein dispatched homolog 1 [KO:K24680]
109687726  signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
109678160  Boc; brother of CDO isoform X1 [KO:K20020]
109698467  Cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
109674444  Gas1; LOW QUALITY PROTEIN: growth arrest-specific protein 1 [KO:K06232]
109689214  Lrp2; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 2 [KO:K06233]
109686285  CUNH16orf52; uncharacterized protein C16orf52 homolog [KO:K23663]
109691883  Megf8; LOW QUALITY PROTEIN: multiple epidermal growth factor-like domains protein 8 [KO:K23664]
109694253  Mgrn1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
109684429  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109695587  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109684472  LOW QUALITY PROTEIN: beta-adrenergic receptor kinase 2-like [KO:K00910] [EC:2.7.11.15]
109701375  Grk3; LOW QUALITY PROTEIN: beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
109690706  Grk2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
109695695  Evc; LOW QUALITY PROTEIN: ellis-van Creveld syndrome protein [KO:K19605]
109695698  Evc2; limbin [KO:K19608]
109674500  Efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
109683405  Iqce; LOW QUALITY PROTEIN: IQ domain-containing protein E [KO:K24677]
109697447  Arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
109680800  Arrb1; beta-arrestin-1 isoform X1 [KO:K04439]
109694180  Kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
109699513  Cul3; cullin-3 isoform X1 [KO:K03869]
109701282  Spopl; speckle-type POZ protein-like isoform X1 [KO:K10523]
109691397  Spop; speckle-type POZ protein [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
ccan04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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