On the possible participation of phosphatidylinositol-3-kinase in activation by insulin and epidermal growth factor phospholipase c, hydrolyzing glycosylphosphatidylinositol

Abstract

The pleiotropic effect of insulin is based on signal transfer from insulin receptor to a series of intracellular effector systems, one of which is glycosyl phosphatidyl inositol (GPI) specific phospholipase C (PLC), hydrolyzing membranous inositol-containing glycophospholipids to produce diacylglycerol, a phospholipase C activator, and inositolphosphoglycane (IPG), a probable secondary messenger in transfer of insulin metabolic signal. For disclosing the mechanisms of GPI-PLC conjugation with insulin receptors and growth factors, we analyzed GPI hydrolysis in Rati cells and found that insulin and epidermal growth factors (EGF) activate GPI hydrolysis to IPG by 20 and 40%o, respectively (p<0.001), while specific phosphatidylinositol- 3’-kinase (PIj kinase) inhibitor vortmannin cancels this insulin and EGF effect. These data permit us to hypothesize the participation of PIj kinase in signal transfer from insulin and EGF receptor GPI-PLC.