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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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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)
  • Received : 2011.05.30
  • Accepted : 2011.07.08
  • Published : 2011.09.30
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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.

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References

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