title: Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death.
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.
authors.affiliation: Department of Biochemistry, School of Medicine, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Byoung Hee
authors.initials: BH
authors.lastname: Park
authors.forename: Yong Hee
authors.initials: YH
authors.lastname: Lee
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D013058:Mass Spectrometry; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D018631:ras Proteins; C415864:SAV1 protein, human; C109163:STK24 protein, human; D000099317:Hippo Kinases; C097835:STK3 protein, human