PYK2 IS A DOWNSTREAM MEDIATOR OF THE IL-2 RECEPTOR-COUPLED JAK SIGNALING PATHWAY

Many cytokines transmit signals to the cell interior through activatio n of receptor-associated, Janus family protein tyrosine kinases (Jak P TKs). The interleukin-2 receptor (IL-2R) is associated with the Jak1 a nd Jak3 PTKs, and ligand-induced activation of these PTKs is essential for lymphocyte proliferation. Here, the nonreceptor PTK, Pyk2, was fo und to be activated following IL-2 stimulation in a Jak-dependent mann er. Furthermore, physical association was detected between endogenous Pyk2 and Jak3, and a dominant interfering mutant of Pyk2 inhibited IL- 2-induced cell proliferation without affecting Stat5 activation. Colle ctively, these results suggest that Pyk2 is a newly identified compone nt of the Jak-mediated IL-2 signaling pathway.