Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase
Koskinen PJ; Rainio EM; Sandholm J
Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase
Koskinen PJ
Rainio EM
Sandholm J
AMER ASSOC IMMUNOLOGISTS
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042718100
https://urn.fi/URN:NBN:fi-fe2021042718100
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]