Reactome | Phosphorylated SMO changes conformation and is activated

Phosphorylated SMO changes conformation and is activated

Stable Identifier

R-DME-216202

Type

Reaction [transition]

Species

Drosophila melanogaster

Compartment

plasma membrane

ReviewStatus

5/5

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Phosphorylated SMO changes conformation and is activated

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The Smoothened (SMO) large terminal cytoplasmic domain changes conformation in response to phosphorylation and becomes active. The localisation of SMO and its partners shifts from internal vesicles towards the plasma membrane. SMO stability increases results in the SMO:COS:FU:CI complexes at the plasma membrane becoming more abundant.

Activation of SMO leads to reduced association of the Ser/Thr protein kinases: Protein kinase A (PKA-C1), Shaggy (SGG), Casein kinase 1 alpha (CKIalpha), and Casein kinase I epsilon (DCO) with Costal2 (COS). This leads to a reduced phosphorylation of Cubitus Interruptus (CI) and inhibition of CI proteolysis and processing. This increases full-length CI protein levels.

Literature References

PubMed ID	Title	Journal	Year
15691767	Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus Tong, C, Wang, G, Zhang, W, Zhao, Y, Wang, B, Jiang, J, Jia, J	Dev Cell	2005
17925225	Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation Smelkinson, MG, Kalderon, D, Zhou, Q	Dev Cell	2007
10966113	Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened Cohen, SM, Denef, N, Neubüser, D, Perez, L	Cell	2000
15616566	Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I Tong, C, Wang, B, Jiang, J, Luo, L, Jia, J	Nature	2004
17960137	Hedgehog regulates smoothened activity by inducing a conformational switch Tong, C, Jiang, J, Zhao, Y	Nature	2007