Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death
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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. [BMB reports 2011; 44(9): 584-589]
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. [BMB reports 2011; 44(9): 584-589]
참고문헌 (26)
- Zeng, Q, "The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals", Cancer Cell, 13, pp.188~192 (2008)
- Radu, M, "The DeMSTification of mammalian Ste20 kinases", Curr. Biol, 19, pp.R421~R425 (2009)
- Graves, J. D, "Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1", EMBO J, 17, pp.2224~2234 (1998)
- Ura, S, "MST1-JNK promotes apoptosis via caspase-dependent and independent pathways", Genes Cells, 6, pp.519~530 (2001)
- Choi, J, "Mst1-FoxO Signaling Protects Naive T Lymphocytes from Cellular Oxidative Stress in Mice", PLOS ONE, 4, pp.e8011~ (2009), PLoS
- Katagiri, K, "Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes", EMBO J, 28, pp.1319~1331 (2009)
- Oh, S, "Crucial Role for Mst1 and Mst2 Kinases in Early Embryonic Development of the Mouse", MOLECULAR AND CELLULAR BIOLOGY, 29(23), pp.6309~6320 (2009), AMER SOC MICROBIOLOGY
- Hao, Y, "Tumor suppressor LATS1 is a negative regulator of oncogene YAP", J. Biol. Chem, 283, pp.5496~5509 (2008)
- 김정목, "Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control", GENES DEVELOPMENT, 21(21), pp.2747~2761, COLD SPRING HARBOR LAB PRESS
- Huang, J, "The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP", Cell, 122, pp.421~434 (2005)
- Lehtinen, M. K, "A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span", Cell, 125, pp.987~1001 (2006)
- Yuan, Z, "Regulation of neuronal cell death by MST1-FOXO1 signaling", J. Biol. Chem, 284, pp.11285~11292 (2009)
- Ahn, S. H, "Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide- induced apoptosis in S", cerevisiae. Cell, 120, pp.25~36 (2005)
- Cheung, W. L, "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase", Cell, 113, pp.507~517 (2003)
- Chan, E. H, "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1", Oncogene, 24, pp.2076~2086 (2005)
- Wu, S, "hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts", Cell, 114, pp.445~456 (2003)
- Lee, J. H, "A crucial role of WW45 in developing epithelial tissues in the mouse", EMBO Journal, 27(8), pp.1231~1242 (2008), Nature Publishing Group
- Hwang, E, "Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway", Proc. Natl. Acad. Sci. U. S. A, 104, pp.9236~9241 (2007)
- Tapon, N, "Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines", Cell, 110, pp.467~478 (2002)
- Callus, B. A, "Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation", FEBS J, 273, pp.4264~4276 (2006)
- Oppermann, F. S, "Largescale proteomics analysis of the human kinome", Mol. Cell. Proteomics, 8, pp.1751~1764 (2009)
- Gnad, F, "PHOSIDA (phosphorylation site database): management, structural and evolutionary investigation, and prediction of phosphosites", Genome Biol, 8, pp.R250~ (2007)
- Burgermeister, E, "Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma", Mol. Cell. Biol, 27, pp.803~817 (2007)
- Yuan, Z, "Phosphoinositide 3-kinase", Akt inhibits MST1-mediated proapoptotic signaling through phosphorylation of threonine 120, 2010, pp.285, 3815~3824
- Khokhlatchev, A, "Identification of a novel Ras-regulated proapoptotic pathway", Curr. Biol, 12, pp.253~265 (2002)
- Rabizadeh, S, "The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death", J. Biol. Chem, 279, pp.29247~29254 (2004)