Entry Name Hedgehog signaling pathway
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 transductionBRITE hierarchy
Pathway map Orthology K02161 BCL2; apoptosis regulator Bcl-2
K03362 FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K04503 CCND1; G1/S-specific cyclin-D1
K06229 SUFU; suppressor of fused
K06230 GLI3; zinc finger protein GLI3
K06231 HHIP; hedgehog interacting protein
K06232 GAS1; growth arrest-specific 1
K06233 LRP2; low density lipoprotein-related protein 2
K08439 GPR161; G protein-coupled receptor 161
K10151 CCND2; G1/S-specific cyclin-D2
K10394 KIF3A; kinesin family member 3A
K10523 SPOP; speckle-type POZ protein
K16797 GLI1; zinc finger protein GLI1
K16798 GLI2; zinc finger protein GLI2
K18806 KIF7; kinesin family member 7
K19605 EVC1; ellis van creveld syndrome protein 1
K19608 EVC2; ellis van creveld syndrome protein 2
K20033 CDON, CDO; cell adhesion molecule-related/down-regulated by oncogenes
K23663 MOSMO; modulator of smoothened protein
K23664 MEGF8; multipile epidermal growth factor-like domains protein 8
K23852 EFCAB7; EF-hand calcium-binding domain-containing protein 7
K24677 IQCE; IQ domain-contaning protein E
K24678 HHAT; protein-cysteine N-palmitoyltransferase HHAT
K24679 HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein
K24680 DISP1; protein dispatched 1
K24706 SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2
Compound Reference Authors Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
Title Hedgehog receptor function during craniofacial development.
Journal Reference Authors Briscoe J, Therond PP
Title The mechanisms of Hedgehog signalling and its roles in development and disease.
Journal Reference Authors Alman BA
Title The role of hedgehog signalling in skeletal health and disease.
Journal 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 Reference Authors Sasai N, Briscoe J
Title Primary cilia and graded Sonic Hedgehog signaling.
Journal Reference Authors Heretsch P, Tzagkaroulaki L, Giannis A
Title Modulators of the hedgehog signaling pathway.
Journal Reference Authors Anderson E, Peluso S, Lettice LA, Hill RE
Title Human limb abnormalities caused by disruption of hedgehog signaling.
Journal Reference Authors Rohatgi R, Scott MP
Title Cell biology. Arrestin' movement in cilia.
Journal 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 Reference Authors Ok CY, Singh RR, Vega F
Title Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
Journal Reference Authors Hsia EY, Gui Y, Zheng X
Title Regulation of Hedgehog signaling by ubiquitination.
Journal 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 Reference 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 Reference 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 Related ko04120 Ubiquitin mediated proteolysis
