This is a revised application for a FIRST Award which proposes to study the role of phosphatidylinositol 3-kinase (PI3K) in platelet signal transduction. PI3K is a cytosolic lipid kinase that phosphorylates the D-3 hydroxyl position of the inositide ring of PI, leading to the formation of 3- phospho-PI's. Little is known about the role of this enzyme in platelet signal-response coupling. The P.I. proposes to study this problem first by determining how thrombin-induced PI3K activation plays a functional role in the platelet responses of secretion and aggregation. Second, studies are proposed to identify the cytoskeletal proteins and kinases that interact with PI3K and to determine the nature of these interactions. Finally, based on earlier observations by others, experiments will be performed to determine whether the small GTP-binding protein, rhoA, associates with and regulates PI3K activity in platelets.
| Gentilini, G; Kirschbaum, N E; Augustine, J A et al. (1999) Inhibition of human umbilical vein endothelial cell proliferation by the CXC chemokine, platelet factor 4 (PF4), is associated with impaired downregulation of p21(Cip1/WAF1). Blood 93:25-33 |
| Geltz, N R; Augustine, J A (1998) The p85 and p110 subunits of phosphatidylinositol 3-kinase-alpha are substrates, in vitro, for a constitutively associated protein tyrosine kinase in platelets. Blood 91:930-9 |
