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http://dx.doi.org/10.5483/BMBRep.2011.44.9.584

Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death  

Park, Byoung-Hee (Department of Biochemistry, School of Medicine, Chungbuk National University)
Lee, Yong-Hee (Department of Biochemistry, School of Medicine, Chungbuk National University)
Publication Information
BMB Reports / v.44, no.9, 2011 , pp. 584-589 More about this Journal
Abstract
The mammalian ste20-like kinase (MST) pathway is important in the regulation of apoptosis and cell cycle and emerges as a novel tumor suppressor pathway. MST-induced phosphorylation of Salvador homolog 1 (SAV1), which is a scaffold protein, has not been evaluated in detail. We performed a mass spectrometric analysis of the SAV1 protein that was co-expressed with MST2. Phosphorylation was detected at Thr-26, Ser-27, Ser-36 and Ser-269. Although single or double mutations had little effects, the mutation of all four residues in SAV1 to Ala (SAV1-4A) had inhibitory effects on the MST pathway. MST2-mediated induction of SAV1-4A protein levels, SAV1-4A interaction with MST2 and the self-dimerization of SAV1-4A were weaker compared to those of wild-type SAV1. SAV1-4A inhibited MST2- and K-RasG12V-induced cell death of MCF7 cells. These results suggest that MST-mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway.
Keywords
Cell death; Hippo; MST; Phosphorylation; SAV1;
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