COT KINASE REGULATION OF IL-2 PRODUCTION IN JURKAT T-CELLS

tpl-2 is a rat gene that encodes a serine/threonine protein kinase tha t can act as a novel mitogen-activated protein (MAP) kinase kinase kin ase. Tpl-2 is activated in Moloney murine leukemia virus-induced rat T lymphomas, due to a truncation in the C-terminal region of the protei n. 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 ac tivity than the nontruncated form. In this paper we show that an incre ase in truncated Cot kinase expression correlates with an increase in IL-2 production in anti-CD3-treated Jurkat cells. Truncated Cot expres sion also cooperates with PHA or phorbol 12,13-dibutyrate (PDBu) and c alcium ionophore for IL-2 production in Jurkat cells. Both the truncat ed and nontruncated Cot forms increased IL-2 transcription because the y enhanced transcription of a reporter gene linked to the IL-2 promote r. The expression of a dominant negative form of Cot inhibits transcri ption 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 r ole in Moloney murine leukemia virus-induced lymphomagenesis.