Cot kinase regulation of IL-2 production in Jurkat T cells.
tpl-2 is a rat gene that encodes a serine/threonine protein kinase that can act as a novel mitogen-activated protein (MAP) kinase kinase kinase. Tpl-2 is activated in Moloney murine leukemia virus-induced rat T lymphomas, due to a truncation in the C-terminal region of the protein. cot is a very closely related gene, if not the human homologue. The truncated form of Cot has been shown to have a higher transforming activity than the nontruncated form. In this paper we show that an increase in truncated Cot kinase expression correlates with an increase in IL-2 production in anti-CD3-treated Jurkat cells. Truncated Cot expression also cooperates with PHA or phorbol 12,13-dibutyrate (PDBu) and calcium ionophore for IL-2 production in Jurkat cells. Both the truncated and nontruncated Cot forms increased IL-2 transcription because they enhanced transcription of a reporter gene linked to the IL-2 promoter. The expression of a dominant negative form of Cot inhibits transcription directed by the IL-2 promoter in Jurkat cells stimulated by PDBu and ionophore. These data suggest a role of Tpl-2/Cot kinase in IL-2 production during T lymphocyte activation and could also explain its role in Moloney murine leukemia virus-induced lymphomagenesis.
Ballester
A
A
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Facultad de Medicina Universidad Autónoma de Madrid, Spain.
Tobeña
R
R
Lisbona
C
C
Calvo
V
V
Alemany
S
S
D017252:CD3 Complex / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D020930:MAP Kinase Kinase Kinases; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014162:Transfection
D017252:CD3 Complex; D007376:Interleukin-2; D007476:Ionophores; D011518:Proto-Oncogene Proteins; D015240:Phorbol 12,13-Dibutyrate; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human