Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

There are five isoforms of the regulatory subunit for the heterodimeric typ e of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own t yrosine phosphorylations and associations with various tyrosine kinase rece ptors were investigated. When overexpressed in CHO-PDGFR cells, the associa tions of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar, However, when overexpressed in CHO-IR cells, p55 gamma exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms, Fu rthermore, p55 alpha and p55 gamma were found to be tyrosine-phosphorylated . Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cell s and stimulated with epidermal growth factor (EGF), phosphorylated EGF rec eptor was detected in p85 alpha, p85 beta and p50 alpha immunoprecipitates, but not in p55 alpha and p55 gamma immunoprecipitates. In addition, EGF-in duced tyrosine phosphorylation was observed in p85 alpha, p85 beta, p55 alp ha and p55 gamma, but not in p50 alpha, immunoprecipitates. Thus, each regu latory subunit exhibits specific responses regarding both the association w ith tyrosine-phosphorylated substrates and its own tyrosine phosphorylation . These results suggest that each isoform possesses specific roles in signa l transduction, based on its individual tyrosine kinase receptor, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.