tailieunhanh - Báo cáo khoa học: Receptor association and tyrosine phosphorylation of S6 kinases

Ribosomal protein S6 kinase (S6K) is activated by an array of mitogenic stimuli and is a key player in the regulation of cell growth. The activation process of S6 kinase involves a complex and sequential series of multiple Ser⁄Thr phosphorylations and is mainly mediated via phosphatidylinositol 3-kinase (PI3K)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and mTor-dependent pathways. | ềFEBS Journal Receptor association and tyrosine phosphorylation of S6 kinases Heike Rebholz1 2 Ganna Panasyuk3 Timothy Fenton1 2 Ivan Nemazanyy3 Taras Valovka4 Marc Flajolet5 Lars Ronnstrand6 Len Stephens7 Andrew West7 and Ivan T. Gout2 3 1 Ludwig Institute for Cancer Research London UK 2 Department of Biochemistry and Molecular Biology University College London UK 3 The Institute of Molecular Biology and Genetics Kyiv Ukraine 4 Institute of Veterinary Biochemistry and Molecular Biology University Zurich Switzerland 5 Rockefeller University New York NY USA 6 Lund University Department of ExperimentalClinicalChemistry Malmo Sweden 7 Babraham Institute Cambridge UK 8 GlaxoSmithKline Harlow UK Keywords AGC kinases platelet-derived growth factor receptor receptor tyrosine kinases ribosomal protein S6 kinase src Correspondence H. Rebholz Box 296 Rockefeller University 1230 York Ave New York NY 10021 USA Fax 1 212 327 7888 Tel 1 212 327 8486 E-mail hrebholz@ Received 17 August 2005 revised 6 February 2006 accepted 8 March 2006 doi Ribosomal protein S6 kinase S6K is activated by an array of mitogenic stimuli and is a key player in the regulation of cell growth. The activation process of S6 kinase involves a complex and sequential series of multiple Ser Thr phosphorylations and is mainly mediated via phosphatidylinositol 3-kinase PI3K -3-phosphoinositide-dependent protein kinase-1 PDK1 and mTor-dependent pathways. Upstream regulators of S6K such as PDK1 and protein kinase B PKB Akt . are recruited to the membrane via their pleckstrin homology PH or protein-protein interaction domains. However the mechanism of integration of S6K into a multi-enzyme complex around activated receptor tyrosine kinases is not clear. In the present study we describe a specific interaction between S6K with receptor tyrosine kinases such as platelet-derived growth factor receptor PDGFR . The interaction with PDGFR is mediated via the kinase or the .