TYROSINE PHOSPHORYLATION OF PYK2 IS SELECTIVELY REGULATED BY FYN DURING TCR SIGNALING

The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexp ressed in T cells and perform crucial functions involved in the initia tion of T cell antigen receptor (TCR) signal transduction. However, th e mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in th e tyrosine phosphorylation of the TCR-zeta chain and the ZAP-70 PTK. I n an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We dem onstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectiv ely dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cell s, coexpression of Pyk2 with Fyn but not Lck resulted in substantial i ncreases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the pref erential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstr ate that Pyk2 is a specific target regulated by Fyn during TCR signali ng.