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 in sulin and epidermal growth factor (EGF). Methods Phosphorylated MAPK, Akt (also termed protein kinase B) and total protein level of MAPK were d etermined by Western blotting using phospho- or non-phospho-state specific an tibodies;the roles of PI3K in these signaling transduction pathways were assess ed by use of PI3K specific inhibitor wortmannin.Results Both in sulin and EGF rapidly stimulated MAPK phosphorylation; wortmannin totally blocke d the MAPK phosphorylation stimulated by insulin, but not by EGF.By contrast, wo rtmannin equally inhibited Akt phosphorylation stimulated by both insulin and EG F. 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 concentrat ions of EGF.Conclusion PI3K plays different roles in the MAPK a ctivation induced by insulin and EGF.