KEGG   PATHWAY: mmu04340Help
mmu04340                    Pathway                                

Hedgehog signaling pathway - Mus musculus (mouse)
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.
Environmental Information Processing; Signal transduction
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Pathway map
mmu04340  Hedgehog signaling pathway

Ortholog table
mmu_M00678  Hedgehog signaling [PATH:mmu04340]
Mus musculus (mouse) [GN:mmu]
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:]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:]
93687  Csnk1a1; casein kinase 1, alpha 1 [KO:K08957] [EC:]
103236  Csnk1g2; casein kinase 1, gamma 2 [KO:K08958] [EC:]
214897  Csnk1g1; casein kinase 1, gamma 1 [KO:K08958] [EC:]
70425  Csnk1g3; casein kinase 1, gamma 3 [KO:K08958] [EC:]
104318  Csnk1d; casein kinase 1, delta [KO:K08959] [EC:]
27373  Csnk1e; casein kinase 1, epsilon [KO:K08960] [EC:]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
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]
20423  Shh; sonic hedgehog [KO:K11988]
16147  Ihh; Indian hedgehog [KO:K11989]
13363  Dhh; desert hedgehog [KO:K11990]
117606  Boc; biregional cell adhesion molecule-related/down-regulated by oncogenes (Cdon) binding protein [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]
66313  Smurf2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:]
75788  Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:]
110355  Grk2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:]
320129  Grk3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:]
59056  Evc; EvC ciliary complex subunit 1 [KO:K19605]
68525  Evc2; EvC ciliary complex subunit 2 [KO:K19608]
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 POZ protein [KO:K10523]
76857  Spopl; speckle-type POZ protein-like [KO:K10523]
C00575  3',5'-Cyclic AMP
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
Hedgehog receptor function during craniofacial development.
Dev Biol 415:198-215 (2016)
Briscoe J, Therond PP
The mechanisms of Hedgehog signalling and its roles in development and disease.
Nat Rev Mol Cell Biol 14:416-29 (2013)
Alman BA
The role of hedgehog signalling in skeletal health and disease.
Nat Rev Rheumatol 11:552-60 (2015)
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
Hedgehog and Resident Vascular Stem Cell Fate.
Stem Cells Int 2015:468428 (2015)
Sasai N, Briscoe J
Primary cilia and graded Sonic Hedgehog signaling.
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
Heretsch P, Tzagkaroulaki L, Giannis A
Modulators of the hedgehog signaling pathway.
Bioorg Med Chem 18:6613-24 (2010)
Anderson E, Peluso S, Lettice LA, Hill RE
Human limb abnormalities caused by disruption of hedgehog signaling.
Trends Genet 28:364-73 (2012)
Rohatgi R, Scott MP
Cell biology. Arrestin' movement in cilia.
Science 320:1726-7 (2008)
Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.
Elife 3:e02555 (2014)
Ok CY, Singh RR, Vega F
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
Am J Pathol 180:2-11 (2012)
Hsia EY, Gui Y, Zheng X
Regulation of Hedgehog signaling by ubiquitination.
Front Biol (Beijing) 10:203-220 (2015)
KO pathway

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