Structural Basis of Human p70 Ribosomal S6 Kinase 1 Regulation by Activation Loop Phosphorylation英文文献.pdfVIP

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 285, NO. 7, pp. 4587–4594, February 12, 2010 © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. Structural Basis of Human p70 Ribosomal S6 Kinase-1 Regulation by Activation Loop Phosphorylation Received for publication, July 2, 2009, and in revised form, October 16, 2009 Published, JBC Papers in Press, October 28, 2009, DOI 10.1074/jbc.M109.040667 ‡1 § § ¶ § ‡ § Tomoko Sunami , Noel Byrne , Ronald E. Diehl , Kaoru Funabashi , Dawn L. Hall , Mari Ikuta , Sangita B. Patel , § § ¶ § ‡ Jennifer M. Shipman , Robert F. Smith , Ikuko Takahashi , Joan Zugay-Murphy , Yoshikazu Iwasawa , Kevin J. Lumb§ § §2 , Sanjeev K. Munshi , and Sujata Sharma From the Departments of ‡Chemistry and ¶Cancer Research, Tsukuba Research Institute, Banyu Pharmaceutical Company, Limited, Tsukuba, Ibaraki, 300-2611, Japan and §Global Structural Biology, Merck Research Laboratories, West Point, Pennsylvania 19486 p70 ribosomal S6 kinase (p70S6K) is a downstream effector of RPS6KB2), respectively (1, 2). RPS6KB1 encodes two isoforms the mTOR signaling pathway involved in cell proliferation, cell that differ only at the N termini by 23 amino acid residues (2). growth, cell-cycle progression, and glucose homeostasis. Multi- The longer form of S6K1 contains an N-terminal nuclear local- ple phosphorylation events with