Open AccessInterleukin 2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin.
Author(s) -
Vı́ctor Calvo,
Craig M. Crews,
Terry A. Vik,
Barbara E. Bierer
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.16.7571
Subject(s) - kinase , ribosomal s6 kinase , biology , tyrosine kinase , microbiology and biotechnology , mitogen activated protein kinase , mapk14 , map2k7 , biochemistry , phosphorylation , p70 s6 kinase 1 , mitogen activated protein kinase kinase , signal transduction , cyclin dependent kinase 2 , protein kinase a , protein kinase b
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.