We identified arginine vasopressin (AVP) as a potent activator of TPA-response element (TRE)-dependent gene expression in rat 3Y1 fibroblasts. In order to examine the involvement of phosphatidylinositol 3-kinase (PI3-kinase) in TRE-mediated gene expression, we examined the effect of the overexpression of PI3-kinase mutant. The overexpression of p110 alpha, the catalytic subunit of PI3-kinase, enhances TRE-reporter expression in response to AVP. On the other hand, the overexpression of the p110-EcoS mutant, which contains the binding site for the regulatory p85 subunit but lacks the catalytic domain, results in decreased TRE reporter expression in response to AVP. These results suggest that PI3-kinase is involved in TRE-dependent gene expression in response to AVP.