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The Journal of Immunology, 2002, 168: 1524-1527.
Copyright © 2002 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Transcriptional Activity of NFATc1 Is Enhanced by the Pim-1 Kinase1

Eeva-Marja Rainio*,{dagger}, Jouko Sandholm* and Päivi J. Koskinen2,*

* Turku Centre for Biotechnology, University of Turku/Åbo Akademi University, and {dagger} Turku Graduate School of Biomedical Sciences, Turku, Finland

Pim-1 is an oncogenic serine/threonine kinase implicated in cytokine-induced signal transduction and in development of lymphoid malignancies. However, its precise function as well as physiological substrates have remained unknown. In this study we demonstrate that Pim-1 can physically interact with the NFATc1 transcription factor and phosphorylate it in vitro on several serine residues. In contrast to previously recognized NFATc kinases, wild-type Pim-1 enhances NFATc-dependent transactivation and IL-2 production in Jurkat T cells, while kinase-deficient Pim-1 mutants inhibit them in a dominant negative fashion. Our results reveal a novel, phosphorylation-dependent regulatory mechanism targeting NFATc1 through which Pim-1 acts as a downstream effector of Ras to facilitate IL-2-dependent proliferation and/or survival of lymphoid cells.




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