Phosphorylation of paxillin by JNK and p38 is essential for full T lymphocyte activation

Abstract

Paxillin is a focal adhesion complex‐assciated adaptor protein, and is regulated by phosphorylation at tyrosine and serine/threonine. Recent studies have revealed a critical role for phosphorylation of paxillin by JNK and p38 MAPK in epithelial cells and neurites. In this study, we examined the requirement of paxillin phosphorylation by p38 MAPK or JNK in T cells using paxillin with mutations at the respective phosphorylation sites, Ser‐85 and Ser‐178. Surprisingly, [S85A]‐paxillin or [S185A]‐paxillin did not interfere with T cell migration and integrin‐mediated T cell adhesion. Neither was T cell receptor‐stimulated activation affected by [S85A]‐paxillin or [S185A]‐paxillin. Interestingly, [S85A/S178A]‐paxillin, mutatant at phosphorylation sites for both p38 and JNK, effectively suppressed T cell activation, but not migration and adhesion. The profound inhibitory effect of [S85A/S178A]‐paxillin in T cell activation was also found in normal T lymphocytes using transgenic mice expressing [S85A/S178A]‐paxillin. Our results demonstrate an unexpected role of paxillin phosphorylation in T cell, whereas phosphorylation by JNK and p38 MAPK is dispensable for T cell motility and adhesion, it is essential for full T cell activation.