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

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-02, Vol.168 (4), p.1524-1527
Main Authors: Rainio, Eeva-Marja, Sandholm, Jouko, Koskinen, Paivi J
Format: Article
Language:English
Subjects:
Animals
COS Cells
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Humans
Interleukin-2 - biosynthesis
Jurkat Cells
Mutation
NFATC Transcription Factors
Nuclear Proteins
Phosphorylation
Phosphoserine - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - physiology
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-pim-1
Proto-Oncogene Proteins p21(ras) - metabolism
Signal Transduction
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
Transcription Factors - chemistry
Transcription Factors - metabolism
Transcriptional Activation
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.4.1524