Two-dimensional analysis of interleukin 2-regulated tyrosine kinase activation mediated by the p70-75 beta subunit of the interleukin 2 receptor.
The proliferation of activated T lymphocytes is dependent on the interaction of the polypeptide growth factor interleukin 2 (IL 2) with its heterodimeric receptor, which consists of a p55 alpha subunit and a p70-75 beta subunit. Previously, it was shown that IL 2 stimulates rapid serine phosphorylation of several membrane and cytysolic proteins. Here, using anti-phosphotyrosine antibodies to purify phosphotyrosyl proteins and two-dimensional gel analysis, we show that IL 2 stimulates rapid tyrosine phosphorylation of a variety of cellular proteins, including pp180, pp92, and pp42 in activated human T lymphocytes. In addition, we have examined IL 2-induced tyrosine phosphorylation in the human cell line YT2C2 which expresses mostly the beta subunit of the IL 2 receptor and the gibbon cell line MLA-144 which expresses only the beta subunit. In both of these cell lines, IL 2 induced tyrosine phosphorylation of the same proteins phosphorylated in normal human T lymphocytes in response to IL 2. We conclude that the beta subunit is sufficient to induce tyrosine phosphorylation of the normal cellular target substrates involved in signal transduction.
Farrar
W L
WL
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701-1013.
Ferris
D K
DK
D000596:Amino Acids / Q000032:analysis; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*
D000596:Amino Acids; D007376:Interleukin-2; D046911:Macromolecular Substances; D010710:Phosphates; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases