IL-2 regulation of tyrosine kinase activity is mediated through the p70-75 beta-subunit of the IL-2 receptor.
The stimulation of activated human T lymphocytes with IL-2 results in increased tyrosine kinase activity. IL-2 treatment of Tac+ T cells stimulates the rapid phosphorylation of multiple protein substrates at M of 116, 100, 92, 70 to 75, 60, 56, 55, 33, and 32 kDa. Phosphorylation on tyrosine residues was detected by immunoaffinity purification of protein substrates with Sepharose linked antiphosphotyrosine mAb, 1G2. Although phorbol ester stimulated serine phosphorylation of the IL-2R alpha (p55) subunit recognized by alpha TAC mAb, IL-2 did not stimulate any detectable phosphorylation of IL-2R alpha or associated coimmune precipitated proteins. In fact, the tyrosine phosphorylated proteins did not coprecipitate with alpha Tac antibody and similar phosphoproteins were stimulated by IL-2 in IL-2R alpha- human large granular lymphocytes which express only the 70 to 75 kDa IL-2R beta subunit of the high affinity IL-2R. Anti-Tac mAb could inhibit IL-2-stimulated tyrosine phosphorylation in activated T cells, which express both IL-2R subunits that together form the high affinity receptor complex, but not in large granular lymphocytes expressing only the IL-2R beta subunit. The data suggest that IL-2 stimulation of tyrosine kinase activities requires only the IL-2R beta subunit.
Ferris
D K
DK
Program Resources, Inc., Frederick Cancer Research Facility, MD 21701.
Willette-Brown
J
J
Ortaldo
J R
JR
Farrar
W L
WL
D000328:Adult; D000596:Amino Acids / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D009943:Organophosphorus Compounds / Q000032:analysis; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism
D000596:Amino Acids; D007376:Interleukin-2; D009943:Organophosphorus Compounds; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases