IMPAIRED TCR-MEDIATED APOPTOSIS AND BCL-XL EXPRESSION IN T-CELLS LACKING THE STRESS KINASE ACTIVATOR SEK1 MKK4/

The dual specificity kinase SEK1 (MKK4) is a direct activator of stres s-activated protein kinases (SAPIC/JNK) in response to environmental s tresses or mitogenic factors, We show in Sek1(-/-)Rag(-/-) chimeric mi ce that a Sek1 null mutation augments the susceptibility of peripheral T cells to TCR/CD3 religation-induced apoptosis, Sek1(-/-) T cells fa iled to induce expression of the death suppressor Bcl-XL in response t o Ag receptor activation. The Sek1 mutation did not alter the inductio n of apoptosis in response to etoposide, cisplatinum, Adriamycin, and gamma-irradiation, Moreover, we show that CD3 epsilon activation alone lends to SEK1 activation in Sek1(+/+) T cells. These results suggest that SEK1 transduces cellular survival signals during T cell stimulati on.