Differential roles of phosphatidylinositol 3-kinase in mitogen-activated prote in kinase activation by insulin and epidermal growth factor / 中国药理学通报

ABSTRACT

Aim: To investigate the roles of phosphatidylinositol 3-kinase (PI3K) in the mitogen-activated protein kinase (MAPK) activation by insulin and epidermal growth factor (EGF). Methods: Phosphorylated MAPK, Akt (also termed protein kinase B) and total protein level of MAPK were determined by Western blotting using phospho- or non-phospho-state specific antibodies; the roles of PI3K in these signaling transduction pathways were assessed by use of PI3K specific inhibitor wortmannin. Results: Both insulin and EGF rapidly stimulated MAPK phosphorylation; wortmannin totally blocked the MAPK phosphorylation stimulated by insulin, but not by EGF. By contrast, wortmannin equally inhibited Akt phosphorylation stimulated by both insulin and EGF. Moreover, wortmannin inhibited insulin-stimulated MAPK phosphorylation in a concentration-dependent manner, and the inability of wortmannin to inhibit EGF-stimulated MAPK phosphorylation was not changed with the use of low concentrations of EGF. Conclusion: PI3K plays different roles in the MAPK activation induced by insulin and EGF.