THE SMALL GTPASE CDC42 INITIATES AN APOPTOTIC SIGNALING PATHWAY IN JURKAT T-LYMPHOCYTES

Apoptosis plays an important role in regulating development and homeos tasis of the immune system, yet the elements of the signaling pathways that control cell death have not been well defined. When expressed in Jurkat T cells, an activated form of the small GTPase Cdc42 induces c ell death exhibiting the characteristics of apoptosis. The death respo nse induced by Cdc42 is mediated by activation of a protein kinase cas cade leading to stimulation of c-Jun amino terminal kinase (JNK). Apop tosis initiated by Cdc42 is inhibited by dominant negative components of the JNK cascade and by reagents that block activity of the ICE prot ease (caspase) family, suggesting that stimulation of the JNK kinase c ascade can lead to caspase activation. The sequence of morphological e vents observed typically in apoptotic cells is modified in the presenc e of activated Cdc42, suggesting that this GTPase may account for some aspects of cytoskeletal regulation during the apoptotic program. Thes e data suggest a means through which the biochemical and morphological events occurring during apoptosis may be coordinately regulated.