THE CATALYTIC DOMAIN OF PP56(LCK) BUT NOT ITS REGULATORY DOMAIN, IS SUFFICIENT FOR INDUCING IL-2 PRODUCTION

The lymphoid src kinase pp56(lck) has been shown to be essential for t he induction of different T lymphocyte responses, including CD4-mediat ed enhancement of Ag-induced T cell activation, early T cell different iation, induction of IL-2 production, and cytotoxicity, It is assumed that pp56(lck) acts on these processes by phosphorylating substrates. However, it has been recently reported that the NH2 regulatory domain is sufficient to mediate CD4 accessory function. In this report we add ress the contribution of the regulatory and catalytic domains of pp56( lck) to another function of this enzyme independent of CD4: TCR-induce d IL-2 production. Two pp56(lck) mutants lacking either the entire cat alytic domain or the entire NH2 regulatory domain were generated, and their abilities to trigger transactivation of the TCR-regulated nuclea r factor of activated T cells (NF-AT) region of the IL-2 promoter were compared, Only the catalytic, but not the NH2 regulatory, domain of p p56(lck) was able to induce NF-AT region transactivation on its own an d to cooperate with other intracellular signals to trigger this respon se, Moreover, the catalytic domain of pp56(lck) was able to induce IL- 2 cytokine production to an extent similar to that of wild-type pp56(l ck). We conclude that different domains of the pp56(lck) molecule cont ribute to regulate distinct biologic functions. In fact, while the NH2 regulatory domain is sufficient to mediate CD4 accessory function, we show here that the catalytic domain of pp56(lck) is sufficient for in duction of IL-2 production, mimicking TCR ligation.