Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice.
The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells. The p44 MAPK-/- mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensable and p42 MAPK (Erk2) may compensate for its loss. However, in p44 MAPK-/- mice, thymocyte maturation beyond the CD4+CD8+ stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3high). In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells. The p44 MAPK apparently has a specific role in thymocyte development.
Pagès
G
G
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France. gpages@unice.fr
Guérin
S
S
Grall
D
D
Bonino
F
F
Smith
A
A
Anjuere
F
F
Auberger
P
P
Pouysségur
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D018390:Gene Targeting; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D007527:Isoenzymes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate