KEGG   PATHWAY: shr04340
Entry
shr04340                    Pathway                                
Name
Hedgehog signaling pathway - Sarcophilus harrisii (Tasmanian devil)
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
shr04340  Hedgehog signaling pathway
shr04340

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913453  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
100913578  GRK3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
100913731  [KO:K04345] [EC:2.7.11.11]
100914944  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
100915359  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100915381  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
100915481  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100915660  IQCE; IQ domain-containing protein E isoform X4 [KO:K24677]
100915794  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
100915964  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
100916268  CSNK1G2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
100916271  MOSMO; modulator of smoothened protein isoform X1 [KO:K23663]
100916629  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
100916643  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
100917246  IHH; indian hedgehog protein [KO:K11989]
100917462  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100918286  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
100919332  DISP1; protein dispatched homolog 1 [KO:K24680]
100919354  [KO:K08957] [EC:2.7.11.1]
100919435  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
100920192  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100921250  CUL3; cullin-3 [KO:K03869]
100921631  EVC2; limbin isoform X1 [KO:K19608]
100921888  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
100922034  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
100922414  SUFU; suppressor of fused homolog isoform X2 [KO:K06229]
100922651  SPOP; speckle-type POZ protein [KO:K10523]
100922845  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
100923383  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
100924021  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100924173  [KO:K08957] [EC:2.7.11.1]
100924736  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
100925029  SHH; sonic hedgehog protein [KO:K11988]
100925350  HHAT; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678]
100925423  LRP2; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
100925642  BTRC; F-box/WD repeat-containing protein 1A isoform X4 [KO:K03362]
100925763  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X5 [KO:K10604] [EC:2.3.2.27]
100926135  MEGF8; LOW QUALITY PROTEIN: multiple epidermal growth factor-like domains protein 8 [KO:K23664]
100926417  CUL1; cullin-1 [KO:K03347]
100927583  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
100929360  [KO:K04345] [EC:2.7.11.11]
100929554  GLI3; transcriptional activator GLI3 [KO:K06230]
100930638  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
100930912  KIF7; kinesin-like protein KIF7 [KO:K18806]
100931491  GPR161; G-protein coupled receptor 161 [KO:K08439]
100933034  BOC; brother of CDO isoform X2 [KO:K20020]
100934183  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100934585  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100935120  SPOPL; speckle-type POZ protein-like [KO:K10523]
100935413  SMO; smoothened homolog [KO:K06226]
105750662  [KO:K08959] [EC:2.7.11.1]
105751130  [KO:K08957] [EC:2.7.11.1]
111718951  GAS1; growth arrest-specific protein 1 [KO:K06232]
116419215  DHH; desert hedgehog protein [KO:K11990]
116420004  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
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
Reference
  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
  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
shr04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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