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.
Rudel
T
T
The Scripps Research Institute, Department of Immunology, La Jolla, CA 92037, USA.
Zenke
F T
FT
Chuang
T H
TH
Bokoch
G M
GM
D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*; D054462:p21-Activated Kinases
D015853:Cysteine Proteinase Inhibitors; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases