KEGG   PATHWAY: mpah04340
mpah04340                   Pathway                                

Hedgehog signaling pathway - Mus pahari (shrew 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
Pathway map
mpah04340  Hedgehog signaling pathway

Mus pahari (shrew mouse) [GN:mpah]
110333595  Ptch1; protein patched homolog 1 [KO:K06225]
110323075  Ptch2; protein patched homolog 2 isoform X1 [KO:K11101]
110316414  Smo; smoothened homolog [KO:K06226]
110321821  Gpr161; G-protein coupled receptor 161 [KO:K08439]
110337220  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:]
110320995  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
110333354  Csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:]
110326057  Csnk1g2; casein kinase I isoform X1 [KO:K08958] [EC:]
110327644  Csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:]
110333022  Csnk1g3; casein kinase I isoform X1 [KO:K08958] [EC:]
110332251  Csnk1d; casein kinase I isoform X1 [KO:K08959] [EC:]
110334729  casein kinase I [KO:K08960] [EC:]
110329614  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
110326390  Gli1; zinc finger protein GLI1 [KO:K16797]
110321463  Gli2; zinc finger protein GLI2 [KO:K16798]
110333582  Gli3; transcriptional activator GLI3 [KO:K06230]
110318082  Sufu; suppressor of fused homolog isoform X1 [KO:K06229]
110318868  Kif7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
110337499  Hhip; hedgehog-interacting protein [KO:K06231]
110322378  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
110315929  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110321591  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110316251  Cul1; cullin-1 [KO:K03347]
110331061  Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
110337956  Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
110322295  Hhat; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678] [EC:2.3.1.-]
110328114  Hhatl; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
110316392  Shh; sonic hedgehog protein isoform X1 [KO:K11988]
110322250  Ihh; indian hedgehog protein [KO:K11989]
110335174  Dhh; desert hedgehog protein [KO:K11990]
110321849  Disp1; protein dispatched homolog 1 isoform X1 [KO:K24680]
110323472  Scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
110329501  Boc; LOW QUALITY PROTEIN: brother of CDO [KO:K20020]
110327985  Cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
110334027  Gas1; growth arrest-specific protein 1 [KO:K06232]
110318574  Lrp2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
110332555  C1H16orf52; uncharacterized protein C16orf52 homolog [KO:K23663]
110336165  Megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
110329314  Mgrn1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:]
110331264  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:]
110339179  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:]
110312920  Grk3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:]
110312827  Grk2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:]
110330621  Evc; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
110330483  Evc2; limbin [KO:K19608]
110323302  Efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
110312855  Iqce; IQ domain-containing protein E isoform X1 [KO:K24677]
110332625  Arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
110315912  Arrb1; beta-arrestin-1 isoform X1 [KO:K04439]
110331414  Kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
110321212  Cul3; cullin-3 isoform X1 [KO:K03869]
110315153  TD and POZ domain-containing protein 5-like [KO:K10523]
110315178  TD and POZ domain-containing protein 1-like [KO:K10523]
110315761  TD and POZ domain-containing protein 4-like [KO:K10523]
110318345  Spopl; speckle-type POZ protein-like isoform X1 [KO:K10523]
110320660  TD and POZ domain-containing protein 4-like [KO:K10523]
110314747  TD and POZ domain-containing protein 3-like [KO:K10523]
110314748  TD and POZ domain-containing protein 5-like [KO:K10523]
110315536  TD and POZ domain-containing protein 3-like [KO:K10523]
110330610  TD and POZ domain-containing protein 5-like [KO:K10523]
110315023  LOW QUALITY PROTEIN: TD and POZ domain-containing protein 5-like [KO:K10523]
110315025  TD and POZ domain-containing protein 3-like [KO:K10523]
110315881  TD and POZ domain-containing protein 5-like [KO:K10523]
110331187  Spop; speckle-type POZ protein isoform X1 [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)
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
Dev Cell 44:113-129.e8 (2018)
Pusapati GV, Hughes CE, Dorn KV, Zhang D, Sugianto P, Aravind L, Rohatgi R
EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.
Dev Cell 28:483-96 (2014)
Rodgers UR, Lanyon-Hogg T, Masumoto N, Ritzefeld M, Burke R, Blagg J, Magee AI, Tate EW
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
ACS Chem Biol 11:3256-3262 (2016)
mpah04120  Ubiquitin mediated proteolysis
KO pathway

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