AN EGF RECEPTOR-MEDIATED SIGNAL ATTENUATES THE INHIBITORY EFFECT OF LPA ON AN ADENYLATE-CYCLASE ACTIVITY

A tyrosine kinase receptor-mediated and a heterotrimeric G protein-cou pled receptor-mediated signals have been shown to evoke distinct intra cellular signaling events. There has been increasing evidence that cro ss-talk exists between a tyrosine kinase receptor-mediated and a heter otrimeric G protein-coupled receptor-mediated signal transduction path ways. In the present study, we have studied effects of EGF receptor ac tivation on activities of inhibitory G protein (Gi). We show that the amounts of Gi/Go ADP-ribosylated by islet-activating protein (IAP) inc reased by 30-40 % in the membranes of Rat I fibroblast cells pretreate d with EGF compared with those without pretreatment. When an effect of lysophosphatidic acid (LPA) stimulation on an adenylate cyclase activ ity was examined, LPA partly attenuated forskolin-stimulated adenylate cyclase activity via Gi because IAP pretreatment blocked the inhibito ry effect of LPA. Pretreatment with EGF reduced the ability of LPA to inhibit the forskolin-stimulated adenylate cyclase activity, while the pretreatment did not have any effects on the forskolin-stimulated act ivity. Thus, the EGF receptor-mediated signal appears to cause the imp airment of Gi function in Rat 1 fibroblast cells.