Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase



: Rainio EM, Sandholm J, Koskinen PJ

Publisher: AMER ASSOC IMMUNOLOGISTS

: 2002

: Journal of Immunology

: JOURNAL OF IMMUNOLOGY

: J IMMUNOL

: 168

: 4

: 1524

: 1527

: 4

: 0022-1767

DOI: https://doi.org/10.4049/jimmunol.168.4.1524


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.

Last updated on 2024-26-11 at 17:41