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

Alberola-Ila, José and Levin, Steve D. and Barton, Greg and Forbush, Katherine and Zon, Leonard I. and Perlmutter, Roger M. (1998) Analysis of the role of MKK-4/Sek-1 in T cell development and apoptosis. International Immunology, 10 (8). pp. 1077-1082. ISSN 1460-2377. doi:10.1093/intimm/10.8.1077.

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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.

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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.
Funding AgencyGrant Number
Leukemia Society of AmericaUNSPECIFIED
Howard Hughes Medical InstituteUNSPECIFIED
Subject Keywords:apoptosis, dominant-negative transgene, Fas, thymic development, strees-activated proteine kinase
Issue or Number:8
Record Number:CaltechAUTHORS:20200330-072114315
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Official Citation:J Alberola-Ila, S D Levin, G Barton, K Forbush, L I Zon, R M Perlmutter, Analysis of the role of MKK-4/Sek-1 in T cell development and apoptosis., International Immunology, Volume 10, Issue 8, Aug 1998, Pages 1077–1082,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102160
Deposited By: Tony Diaz
Deposited On:30 Mar 2020 15:35
Last Modified:16 Nov 2021 18:09

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