Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B-Reference-Cited by-同舟云学术

Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B

Published:1997-07-25 Issue:5325 Volume:277 Page:567-570
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Stokoe David¹²³⁴⁵,Stephens Leonard R.¹²³⁴⁵,Copeland Terry¹²³⁴⁵,Gaffney Piers R. J.¹²³⁴⁵,Reese Colin B.¹²³⁴⁵,Painter Gavin F.¹²³⁴⁵,Holmes Andrew B.¹²³⁴⁵,McCormick Frank¹²³⁴⁵,Hawkins Phillip T.¹²³⁴⁵

Affiliation:

1. D. Stokoe and F. McCormick, Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.

2. L. R. Stephens and P. T. Hawkins, Babraham Institute, Babraham, CB2 4AT, Cambridge, UK.

3. T. Copeland, ABL-Basic Research Program, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.

4. P. R. J. Gaffney and C. B. Reese, Department of Chemistry, Kings College, London WC2R 2LS, UK.

5. G. F. Painter and A. B. Holmes, Department of Chemistry, Cambridge University, Cambridge CB2 3RA, UK.

Abstract

Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P 3 ]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P 3 was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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