Lysophosphatidic acid (LPA) is known to induce protein tyrosine phosphorylation and has growth factor-like effects. In the last several years, the epidermal growth factor (EGF) receptor has been recognized as a protein tyrosine kinase that plays a central role in mediating LPA-induced tyrosine phosphorylation and Erk MAP kinase activation. In this article, we review recent progress in the study of trans-regulation of EGF receptor by LPA and G protein-coupled receptors (GPCR) and discuss the gap in our knowledge of the mechanism by which LPA induces EGF receptor activation.