KEGG   PATHWAY: tst04340
Entry
tst04340                    Pathway                                
Name
Hedgehog signaling pathway - Trachemys scripta elegans (red-eared slider)
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
tst04340  Hedgehog signaling pathway
tst04340

Organism
Trachemys scripta elegans (red-eared slider) [GN:tst]
Gene
117878979  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
117873915  SMO; smoothened homolog [KO:K06226]
117887299  GPR161; G-protein coupled receptor 161 [KO:K08439]
117881601  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117888473  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
117888475  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
117888815  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117889034  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
117881633  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
117868847  CSNK1G2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
117883894  casein kinase I-like [KO:K08958] [EC:2.7.11.1]
117878714  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
117887125  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
117880440  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
117886617  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117885079  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
117872608  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
117879823  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
117884157  KIF7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
117878500  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
117877043  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
117884539  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
117873081  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
117872629  CUL1; cullin-1 [KO:K03347]
117881050  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
117881595  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
117874413  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
117871947  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
117872034  SHH; sonic hedgehog protein [KO:K11988]
117874486  DISP1; protein dispatched homolog 1 [KO:K24680]
117877200  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
117887113  BOC; LOW QUALITY PROTEIN: brother of CDO [KO:K20020]
117868506  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
117883815  growth arrest-specific protein 1-like [KO:K06232]
117879181  GAS1; growth arrest-specific protein 1 [KO:K06232]
117884845  LRP2; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
117884104  MOSMO; modulator of smoothened protein isoform X1 [KO:K23663]
117884445  MGRN1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
117887821  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
117883541  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117888032  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
117876033  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
117878015  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
117878014  EVC2; limbin isoform X1 [KO:K19608]
117881220  EFCAB7; EF-hand calcium-binding domain-containing protein 7 isoform X1 [KO:K23852]
117883959  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
117871390  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
117881282  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
117882642  CUL3; cullin-3 [KO:K03869]
117869173  SPOP; speckle-type POZ protein [KO:K10523]
117884717  SPOPL; speckle-type POZ protein-like [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
tst04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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