Ligand-stimulated tyrosine phosphorylation of the IL-2 receptor beta chain and receptor-associated proteins.
Interleukin-2 (IL-2) stimulates the rapid phosphorylation on tyrosine of several specific cellular proteins. However, the high-affinity human IL-2 receptor, composed of an alpha (p55) and beta (p70/75) subunit, does not contain a cytoplasmic tyrosine kinase domain. In this study, we investigated the identities of the proteins phosphorylated on tyrosine in response to IL-2 stimulation to examine possible pathways of signal transduction. By the use of immunoblotting with anti-phosphotyrosine antibodies, we demonstrate that IL-2 augments tyrosine phosphorylation of the IL-2 receptor beta chain in human cell lines expressing either high-affinity (alpha/beta) receptors or only the beta chain. In IL-2-dependent mouse T cell lines, a 100,000-Da protein was phosphorylated on tyrosine in response to IL-2 and is proposed to be the mouse IL-2 receptor beta chain. Two other cellular proteins, pp55 and pp105 in human or pp55 and pp115 in mouse cell lines, were phosphorylated on tyrosine in response to IL-2 and coimmunoprecipitated with the high-affinity IL-2 receptor after chemical crosslinking of IL-2-stimulated cells. Thus, the IL-2 receptor may associate with additional subunits or with cellular proteins involved in signal transduction.
Shackelford
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Department of Cancer Biology, Salk Institute, San Diego, California 92186-5800.
Trowbridge
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D000818:Animals; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism*
D007376:Interleukin-2; D011506:Proteins; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases