Inhibition of epidermal growth factor-induced Stat1 activation by lysophosphatidic acid is mediated by pertussis toxin-sensitive G proteins and tyrosine phosphatase in human epidermoid carcinoma A431 cells

We previously reported that pretreatment of A431 cells with G protein-coupled receptor agonists which activate phospholipase C, such as lysophosphatidic acid (LPA), inhibit epidermal growth factor (EGF)-induced formation of Stat1-DNA complex (SIF-C). In this study, we examined the mechanism for this phenomenon. LPA Inhibited EGF-induced but not interferon-gamma-induced SIF-C formation. Ligand-dependent tyrosine phosphorylation of the EGF receptor was markedly reduced by LPA, suggesting that the reduction of the receptor phosphorylation is probably responsible for LPA induced inhibition of SIF-C formation. The LPA action was prevented by pertussis toxin and the tyrosine phosphatase inhibitor vanadate, but not by the phospholipase C inhibitor U-73122. These results demonstrate that the inhibitory effect of LPA on EGF-induced SIF-C formation is mediated by Gi and/or Go proteins and tyrosine phosphatase, but not by Gq proteins coupling with a phospholipase C pathway.