Critical role for Rsk2 in T-lymphocyte activation.
During T-cell activation, a number of cytokine-activated signaling cascades, including the Jak-STAT, phosphoinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase (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 knockout (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 and anti-CD28 stimulation in vitro. Moreover, Rsk2 KO mice had defective homeostatic T-cell expansion following sublethal irradiation in vivo, which is known to involve T-cell receptor (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 nonredundant role of Rsk2 in T-cell activation.
Lin
Jian-Xin
JX
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Spolski
Rosanne
R
Leonard
Warren J
WJ
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D005799:Genes, Dominant / Q000276:immunology; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D053612:Janus Kinases / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012190:Retroviridae; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000276:immunology*; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014161:Transduction, Genetic; D014916:Whole-Body Irradiation
D018106:CD28 Antigens; D017252:CD3 Complex; C508594:IL2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D050791:STAT Transcription Factors; D053612:Janus Kinases; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D048049:Extracellular Signal-Regulated MAP Kinases