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Published August 1998 | public
Journal Article

Analysis of the role of MKK-4/Sek-1 in T cell development and apoptosis

Abstract

The stress-activated protein kinases (SAPK) are a group of dual-specificity kinases with potential roles in the control of apoptosis and proliferation. In most cells they are regulated through phosphorylation by MKK-4. We have investigated the role of MKK-4 in T cell development and function by generating transgenic animals expressing catalytically inactive MKK-4 (dMKK-4) in the thymus. Our results show that overexpression of dMKK-4 does not interfere with normal T cell development. Furthermore, expression of dMKK-4 inhibits Fas- but not phorbol ester plus ionomycin-induced activation of SAPK, suggesting that a SAPK kinase different from MKK-4 is responsible for the regulation of SAPK activation after stimulation of T cells with phorbol ester plus ionomycin. We then analyzed the effect of dMKK-4 on Fas-induced apoptosis of thymocytes. Our results show that activation of SAPK is not a necessary event in Fas-induced apoptosis of thymocytes.

Additional Information

© 1998 Oxford University Press. Received 20 February 1998, accepted 13 April 1998. We thank Xiao Cun Pan for maintaining our animal colony, Dr R. Davis for providing important reagents and our colleagues for helpful discussion. J. A. I. is a Leukemia Society of America special fellow. Part of this work was made while R. M. P. was a HHMI investigator.

Additional details

Created:
August 19, 2023
Modified:
October 19, 2023