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 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.
Mesh Terms:
Animals, COS Cells, DNA-Binding Proteins, Humans, Interleukin-2, Jurkat Cells, Mutation, NFATC Transcription Factors, Nuclear Proteins, Phosphorylation, Phosphoserine, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-pim-1, Proto-Oncogene Proteins p21(ras), Signal Transduction, T-Lymphocytes, Transcription Factors, Transcriptional Activation
Animals, COS Cells, DNA-Binding Proteins, Humans, Interleukin-2, Jurkat Cells, Mutation, NFATC Transcription Factors, Nuclear Proteins, Phosphorylation, Phosphoserine, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-pim-1, Proto-Oncogene Proteins p21(ras), Signal Transduction, T-Lymphocytes, Transcription Factors, Transcriptional Activation
J. Immunol.
Date: Feb. 15, 2002
PubMed ID: 11823475
View in: Pubmed Google Scholar
Download Curated Data For This Publication
5936
Switch View:
- Interactions 2