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Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI

Barry, F. A. and Gibbins, J. M. (2002) Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI. The Journal of Biological Chemistry, 277 (15). pp. 12874-12878. ISSN 1083-351X

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To link to this article DOI: 10.1074/jbc.M200482200

Abstract/Summary

Phosphoinositide 3-kinase (PI3K) is a critical component of the signaling pathways that control the activation of platelets. Here we have examined the regulation of protein kinase B (PKB), a downstream effector of PI3K, by the platelet collagen receptor glycoprotein (GP) VI and thrombin receptors. Stimulation of platelets with collagen or convulxin (a selective GPVI agonist) resulted in PI3K-dependent, and aggregation independent, Ser(473) and Thr(308) phosphorylation of PKBalpha, which results in PKB activation. This was accompanied by translocation of PKB to cell membranes. The phosphoinositide-dependent kinase PDK1 is known to phosphorylate PKBalpha on Thr(308), although the identity of the kinase responsible for Ser(473) phosphorylation is less clear. One candidate that has been implicated as being responsible for Ser(473) phosphorylation, either directly or indirectly, is the integrin-linked kinase (ILK). In this study we have examined the interactions of PKB, PDK1, and ILK in resting and stimulated platelets. We demonstrate that in platelets PKB is physically associated with PDK1 and ILK. Furthermore, the association of PDK1 and ILK increases upon platelet stimulation. It would therefore appear that formation of a tertiary complex between PDK1, ILK, and PKB may be necessary for phosphorylation of PKB. These observations indicate that PKB participates in cell signaling downstream of the platelet collagen receptor GPVI. The role of PKB in collagen- and thrombin-stimulated platelets remains to be determined.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:29065
Uncontrolled Keywords:Haemostasis, thrombosis, platelets, collagen, GPVI
Publisher:American Society for Biochemistry and Molecular Biology

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