Analysis of the role of MKK-4/Sek-1 in T cell development and apoptosis.
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.
Department of Immunology, University of Washington, Seattle 98195, USA.
J
J
Alberola-Ila
S D
SD
Levin
G
G
Barton
K
K
Forbush
L I
LI
Zon
R M
RM
Perlmutter
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D015759:Ionomycin / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation / Q000235:genetics; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019014:fas Receptor; D015759:Ionomycin; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate