CSNK1A1 phosphorylates SMO dimer

Stable Identifier
R-HSA-5632670
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Initial activation of SMO in response to HH occurs with the CSNK1A1-mediated phosphorylation of serine and threonine residues in the C-terminal tail. While many potential CSNK1A1 target residues have been identified in in vitro assays, residues S588, S590, T593 and S595 in the S0 region appear to be the most critical for function (Chen et al, 2011). Initial phosphorylation increases the affinity of the C-terminal tail for both CSNK1A1 and ADRBK1/GRK2, establishing a positive feedback mechanism that promotes further phosphorylation. CSNK1A1 and ADRBK1-mediated phosphorylation is thought to promote an open, activated conformation of the C-terminal tails, analogous to that in Drosophila Smo upon pathway activation (Chen et al, 2011; Chen et al, 2010; Zhao et al, 2007).

Literature References
PubMed ID Title Journal Year
20844016 G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila

Chen, Y, Li, S, Tong, C, Zhao, Y, Wang, B, Liu, Y, Jia, J, Jiang, J

Genes Dev. 2010
21695114 Sonic Hedgehog dependent phosphorylation by CK1? and GRK2 is required for ciliary accumulation and activation of smoothened

Chen, Y, Sasai, N, Ma, G, Yue, T, Jia, J, Briscoe, J, Jiang, J

PLoS Biol. 2011
17960137 Hedgehog regulates smoothened activity by inducing a conformational switch

Zhao, Y, Tong, C, Jiang, J

Nature 2007
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Catalyst Activity
Title
protein serine/threonine kinase activity of SMO dimer:CSNK1A1 [ciliary membrane]
Physical Entity
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