p21-activated kinase (PAK) is required for Fas-induced JNK activation in Jurkat cells.

The process of apoptosis is a critical component of normal immune system development and homeostasis, and in many cells this involves signaling through the c-Jun amino terminal kinase (JNK) pathway. In Jurkat T cells, Fas-induced JNK activity is dependent upon activation of the caspase cascades known to be central components of the apoptotic program. We show in Jurkat cell lines expressing a dominant negative PAK construct that PAK signaling is necessary for JNK activation in response to Fas receptor cross-linking. Inhibition of JNK activation induced by Fas does not impair cell death as assessed by DNA fragmentation. However, expression of the catalytically active C terminus of PAK2, which is generated through caspase action during Fas-mediated apoptosis, induces Jurkat cell apoptosis. We conclude that PAK activity resulting from caspase-mediated cleavage is a necessary component of JNK activation induced by Fas receptor signaling and that PAK2 can contribute to the induction of cell death.