INVOLVEMENT OF THE JAK-3 JANUS KINASE IN SIGNALING BY INTERLEUKIN-2 AND INTERLEUKIN-4 IN LYMPHOID AND MYELOID CELLS

MANY cytokines function through interaction with receptors of the cyto kine receptor superfamily. Although lacking catalytic domains, cytokin e receptors couple ligand binding to induction of protein tyrosine pho sphorylation. Recent studie(1-10) have shown that one or more of the J anus kinase family members (Jaks) associate with cytokine receptors an d are tyrosine phosphorylated and activated following ligand binding. Here we describe a new Jak family kinase, Jak-3, and demonstrate that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and J ak-3 is activated in the responses to interleukin-2 and interleukin-4 in T cells and myeloid cells. Jak-3 activation requires the serine-ric h, membrane-proximal domain of the interleukin-3 receptor beta-chain, but does not require the acidic domain that is required for associatio n and activation of Src family kinases.