The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin

There is extensive evidence to show that phosphatidylinositol 3-kinase play s an important role in signaling by the immune family of receptors, which h as recently been extended to include the platelet collagen receptor, glycop rotein VI, In this report we present two potential mechanisms for the regul ation of this enzyme on stimulation of platelets by collagen. We show that on stimulation with collagen, the regulatory subunit of phosphatidylinosito l 3-kinase associates with the tyrosine-phosphorylated form of the adapter protein linker for activator of T Cells (LAT) and the tyrosine-phosphorylat ed immunoreceptor tyrosine-based activation motif of the Fc receptor gamma- chain (a component of the collagen receptor complex that includes glycoprot ein VI). The associations of the Fc receptor gamma-chain and LAT with p85 a re rapid and supported by the Src-homology 2 domains of the regulatory subu nit. We did not obtain evidence to support previous observations that the r egulatory subunit of phosphatidylinositol 3-kinase is regulated through ass ociation with the tyrosine kinase Syk, The present results provide a molecu lar basis for the regulation of the p85/110 form of phosphatidylinositol 3- kinase by GPVI, the collagen receptor that underlies activation.