The role of ERK5 in T-cell signalling.
The mitogen-activated protein kinase (MAPK) ERK5 plays an important role in mammary epithelial proliferation, endothelial cell survival and normal embryonic development. In nonhaematopoietic cells, mitogenic and stress signals activate the ERK5 cascade. Here, we investigated the role of the ERK5 pathway in T-cell activation and show that primary and leukaemic T cells express ERK5, whose activating phosphorylation is induced by antibodies against CD3 but not by phorbol myristate acetate treatment. ERK5 localized in the cytosol and nucleus in quiescent and activated T cells. In the latter, ERK5 phosphorylation was mainly observed in the nucleus. Selective activation of the ERK5 cascade by transfecting constitutively active MEK5 and wildtype ERK5 induced a reporter gene driven by the IL-2 promoter while barely affecting CD69 expression. These results suggest a new role for the ERK5 cascade in intracellular signalling in T cells.
Garaude
J
J
Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, IFR 122, 34293 Montpellier cedex 5, France.
Kaminski
S
S
Cherni
S
S
Hipskind
R A
RA
Villalba
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099192:CD69 Antigens
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D037181:Lectins, C-Type; D048054:Mitogen-Activated Protein Kinase 7; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens