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. 1992 Aug 15;89(16):7571–7575. doi: 10.1073/pnas.89.16.7571

Interleukin 2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin.

V Calvo 1, C M Crews 1, T A Vik 1, B E Bierer 1
PMCID: PMC49752  PMID: 1380162

Abstract

Binding of interleukin 2 (IL-2) to its receptor generates intracellular signals, including the activation of tyrosine and serine/threonine kinases. In this study the activation of the serine/threonine-specific ribosomal protein S6 kinases in response to IL-2 was analyzed in the murine T-cell line CTLL-20, a model system of IL-2-dependent proliferation. Two major classes of S6 kinases have been characterized: the 90-kDa (rsk) family and the 70-kDa family. In response to the addition of recombinant IL-2, total S6 kinase activity was increased. This S6 kinase activity could not be immunoprecipitated by an antiserum specific for S6 kinases of the 90-kDa family, exhibited a chromatographic behavior characteristic of 70-kDa S6 kinases, and was recognized by a 70-kDa S6 kinase-specific antiserum. Thus, IL-2 binding to its receptor induces specific activation of the 70-kDa family of S6 kinases. Rapamycin, a macrolide immunosuppressant that inhibits IL-2-dependent proliferation, inhibited IL-2-stimulated 70-kDa S6 kinase activity subsequent to early increases in tyrosine kinase activity. These findings imply that the targets of rapamycin include molecules involved in the activation of 70-kDa S6 kinases. These observations further suggest that S6 kinases of the 70-kDa family participate in signal transmission pathways subsequent to IL-2 binding to its receptor.

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Selected References

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