KEGG   PATHWAY: mun04340
Entry
mun04340                    Pathway                                

Name
Hedgehog signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04340  Hedgehog signaling pathway
mun04340

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110551759  Ptch1; protein patched homolog 1 isoform X1 [KO:K06225]
110546514  Ptch2; protein patched homolog 2 [KO:K11101]
110550982  Smo; smoothened homolog [KO:K06226]
110545141  Gpr161; G-protein coupled receptor 161 [KO:K08439]
110564555  cGMP-dependent protein kinase 1 [KO:K04345] [EC:2.7.11.11]
110545842  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110555016  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110546689  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
110552702  Csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
110555594  Csnk1g2; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
110559893  Csnk1g3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
110548832  Csnk1d; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
110564247  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
110561763  Gli1; zinc finger protein GLI1 isoform X1 [KO:K16797]
110546429  Gli2; zinc finger protein GLI2 [KO:K16798]
110550293  Gli3; transcriptional activator GLI3 [KO:K06230]
110556547  Sufu; suppressor of fused homolog isoform X1 [KO:K06229]
110562230  Kif7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
110547836  Hhip; hedgehog-interacting protein [KO:K06231]
110546940  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
110548628  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110547501  Cul1; cullin-1 [KO:K03347]
110547815  Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
110556200  Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
110560215  Shh; sonic hedgehog protein [KO:K11988]
110566358  Ihh; indian hedgehog protein [KO:K11989]
110547394  Dhh; desert hedgehog protein [KO:K11990]
110542356  Boc; brother of CDO isoform X1 [KO:K20020]
110560386  cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
110560391  Cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
110556602  Gas1; growth arrest-specific protein 1 [KO:K06232]
110547796  Lrp2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
110547842  CUNH16orf52; uncharacterized protein C16orf52 homolog isoform X1 [KO:K23663]
110563913  Megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
110545938  Mgrn1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
110547040  Smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
110555644  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
110554001  Grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
110560356  Grk2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
110544913  Evc; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
110544895  Evc2; limbin isoform X1 [KO:K19608]
110560411  Arrb1; beta-arrestin-1 isoform X1 [KO:K04439]
110557323  Arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
110548765  Kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
110552883  Cul3; cullin-3 isoform X1 [KO:K03869]
110556457  speckle-type POZ protein-like isoform X1 [KO:K10523]
110544627  LOW QUALITY PROTEIN: speckle-type POZ protein-like [KO:K10523]
110540843  LOW QUALITY PROTEIN: speckle-type POZ protein B-like [KO:K10523]
110540845  speckle-type POZ protein-like [KO:K10523]
110544797  TD and POZ domain-containing protein 1-like [KO:K10523]
110551210  Spop; speckle-type POZ protein [KO:K10523]
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
Related
pathway
mun04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
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