KEGG   PATHWAY: mmu04340
Entry
mmu04340                    Pathway                                
Name
Hedgehog signaling pathway - Mus musculus (house mouse)
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
mmu04340  Hedgehog signaling pathway
mmu04340

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
19206  Ptch1; patched 1 [KO:K06225]
19207  Ptch2; patched 2 [KO:K11101]
319757  Smo; smoothened, frizzled class receptor [KO:K06226]
240888  Gpr161; G protein-coupled receptor 161 [KO:K08439]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
93687  Csnk1a1; casein kinase 1, alpha 1 [KO:K08957] [EC:2.7.11.1]
103236  Csnk1g2; casein kinase 1, gamma 2 [KO:K08958] [EC:2.7.11.1]
214897  Csnk1g1; casein kinase 1, gamma 1 [KO:K08958] [EC:2.7.11.1]
70425  Csnk1g3; casein kinase 1, gamma 3 [KO:K08958] [EC:2.7.11.1]
104318  Csnk1d; casein kinase 1, delta [KO:K08959] [EC:2.7.11.1]
27373  Csnk1e; casein kinase 1, epsilon [KO:K08960] [EC:2.7.11.1]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
14632  Gli1; GLI-Kruppel family member GLI1 [KO:K16797]
14633  Gli2; GLI-Kruppel family member GLI2 [KO:K16798]
14634  Gli3; GLI-Kruppel family member GLI3 [KO:K06230]
24069  Sufu; SUFU negative regulator of hedgehog signaling [KO:K06229]
16576  Kif7; kinesin family member 7 [KO:K18806]
15245  Hhip; Hedgehog-interacting protein [KO:K06231]
12443  Ccnd1; cyclin D1 [KO:K04503]
12444  Ccnd2; cyclin D2 [KO:K10151]
12043  Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
26965  Cul1; cullin 1 [KO:K03347]
103583  Fbxw11; F-box and WD-40 domain protein 11 [KO:K03362]
12234  Btrc; beta-transducin repeat containing protein [KO:K03362]
226861  Hhat; hedgehog acyltransferase [KO:K24678] [EC:2.3.1.-]
74770  Hhatl; hedgehog acyltransferase-like [KO:K24679]
20423  Shh; sonic hedgehog [KO:K11988]
16147  Ihh; Indian hedgehog [KO:K11989]
13363  Dhh; desert hedgehog [KO:K11990]
68897  Disp1; dispatched RND transporter family member 1 [KO:K24680]
56788  Scube2; signal peptide, CUB domain, EGF-like 2 [KO:K24706]
117606  Boc; BOC cell adhesion associated, oncogene regulated [KO:K20020]
57810  Cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
14451  Gas1; growth arrest specific 1 [KO:K06232]
14725  Lrp2; low density lipoprotein receptor-related protein 2 [KO:K06233]
233812  Mosmo; modulator of smoothened [KO:K23663]
269878  Megf8; multiple EGF-like-domains 8 [KO:K23664]
17237  Mgrn1; mahogunin, ring finger 1 [KO:K10604] [EC:2.3.2.27]
66313  Smurf2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
75788  Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
110355  Grk2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
320129  Grk3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
59056  Evc; EvC ciliary complex subunit 1 [KO:K19605]
68525  Evc2; EvC ciliary complex subunit 2 [KO:K19608]
230500  Efcab7; EF-hand calcium binding domain 7 [KO:K23852]
74239  Iqce; IQ motif containing E [KO:K24677]
109689  Arrb1; arrestin, beta 1 [KO:K04439]
216869  Arrb2; arrestin, beta 2 [KO:K04439]
16568  Kif3a; kinesin family member 3A [KO:K10394]
26554  Cul3; cullin 3 [KO:K03869]
20747  Spop; speckle-type BTB/POZ protein [KO:K10523]
76857  Spopl; speckle-type BTB/POZ protein-like [KO:K10523]
100042761  Tdpoz7; Td and POZ domain containing 7 [KO:K10523]
100043188  Spopfm2; speckle-type BTB/POZ protein family member 2 [KO:K10523]
399674  Tdpoz3; TD and POZ domain containing 3 [KO:K10523]
399675  Tdpoz4; TD and POZ domain containing 4 [KO:K10523]
399676  Tdpoz5; TD and POZ domain containing 5 [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
mmu04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
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