KEGG   PATHWAY: mleu04340
Entry
mleu04340                   Pathway                                
Name
Hedgehog signaling pathway - Mandrillus leucophaeus (drill)
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
mleu04340  Hedgehog signaling pathway
mleu04340

Organism
Mandrillus leucophaeus (drill) [GN:mleu]
Gene
105536603  PTCH1; protein patched homolog 1 [KO:K06225]
105555086  PTCH2; LOW QUALITY PROTEIN: protein patched homolog 2 [KO:K11101]
105550918  SMO; smoothened homolog [KO:K06226]
105539583  GPR161; G-protein coupled receptor 161 isoform X1 [KO:K08439]
105532068  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105540992  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105538055  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105548790  CSNK1A1L; casein kinase I isoform alpha-like [KO:K08957] [EC:2.7.11.1]
105543443  CSNK1A1; casein kinase I isoform alpha isoform X1 [KO:K08957] [EC:2.7.11.1]
105551997  CSNK1G2; casein kinase I isoform gamma-2 [KO:K08958] [EC:2.7.11.1]
105530397  CSNK1G1; casein kinase I isoform gamma-1 isoform X1 [KO:K08958] [EC:2.7.11.1]
105545025  CSNK1G3; casein kinase I isoform gamma-3 isoform X1 [KO:K08958] [EC:2.7.11.1]
105552638  CSNK1D; casein kinase I isoform delta isoform X1 [KO:K08959] [EC:2.7.11.1]
105538880  casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
105544615  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105545574  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
105542064  GLI2; zinc finger protein GLI2 [KO:K16798]
105550240  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
105537791  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
105544077  KIF7; kinesin-like protein KIF7 [KO:K18806]
105544592  HHIP; hedgehog-interacting protein [KO:K06231]
105544506  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105551132  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
105535165  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
105546373  CUL1; cullin-1 [KO:K03347]
105537765  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
105544974  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
105536408  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
105542640  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein [KO:K24679]
105534384  SHH; sonic hedgehog protein [KO:K11988]
105528101  IHH; indian hedgehog protein [KO:K11989]
105544905  DHH; desert hedgehog protein [KO:K11990]
105554496  DISP1; protein dispatched homolog 1 [KO:K24680]
105554004  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 [KO:K24706]
105537563  BOC; brother of CDO [KO:K20020]
105554700  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
105545287  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
105545126  uncharacterized protein C16orf52 homolog [KO:K23663]
105541692  MEGF8; LOW QUALITY PROTEIN: multiple epidermal growth factor-like domains protein 8 [KO:K23664]
105538603  MGRN1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:2.3.2.27]
105551754  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
105543758  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
105536092  ADRBK2; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
105544458  ADRBK1; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
105555311  EVC; ellis-van Creveld syndrome protein [KO:K19605]
105555275  EVC2; limbin [KO:K19608]
105545888  EFCAB7; EF-hand calcium-binding domain-containing protein 7 isoform X1 [KO:K23852]
105537346  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
105539985  ARRB2; beta-arrestin-2 [KO:K04439]
105555216  ARRB1; beta-arrestin-1 [KO:K04439]
105531342  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
105550179  CUL3; cullin-3 isoform X1 [KO:K03869]
105553279  SPOP; speckle-type POZ protein [KO:K10523]
105550226  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
mleu04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
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