Submitted February 5, 2007
Accepted October 5, 2007
Critical role for Rsk2 in T lymphocyte activation
Jian-Xin Lin, Rosanne Spolski, and Warren J. Leonard*
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD
* Corresponding author; email: wjl{at}helix.nih.gov.
During T cell activation, a number of cytokine-activated signaling cascades, including the Jak-STAT, PI 3-kinase, and MAPK pathways, play important roles in modulating the expression of target genes and mediating a cellular response. We now report that interleukin 2 (IL-2) and IL-15, but not IL-7, rapidly activate the p90 ribosomal S6 kinases, Rsk1 and Rsk2 in human T lymphocytes. Surprisingly, mouse spleen T cells transduced with either the wild type or a dominant-negative (DN) Rsk2-expressing retrovirus could not be recovered, in contrast to the normal survival of T cells transduced with retroviruses expressing wild type or DN mutants of Rsk1 or Rsk3. Examination of Rsk2 KO mice revealed normal T cell development, but these T cells had delayed cell cycle progression and lower production of IL-2 in response to anti-CD3 + anti-CD28 stimulation in vitro. Moreover, Rsk2 KO mice had defective homeostatic T cell expansion following sub-lethal irradiation in vivo, which is known to involve TCR, IL-2, and/or IL-15 signals, each of which we demonstrate can rapidly and potently activate Rsk2 in mouse T cells. These results indicate an essential non-redundant role of Rsk2 in T cell activation.
