Murine T-lymphocyte proliferation induced by interleukin 2 correlates with a transient increase in p56lck kinase activity and the tyrosine phosphorylation of a 97-kDa protein.
The addition of recombinant interleukin 2 (rIL-2) to anti-CD3-activated murine G0 phase T cells results in an increased level of tyrosine phosphorylation of a single 97-kDa protein. The degree of tyrosine phosphorylation paralleled the amount of rIL-2 added and correlated with the extent of DNA synthesis. IL-2 treatment resulted in a transient increase in p56lck kinase activity without detectable modification of its level of tyrosine phosphorylation and gel mobility. When G0 T cells were activated by phorbol dibutyrate in the absence of IL-2, the high-affinity IL-2 receptor (IL-2R) expressed failed to induce a proliferative signal, and neither the tyrosine phosphorylation of the 97-kDa protein nor the transient increase in p56lck kinase activity was detected. Northern analysis of the total RNA extracted from these cells showed the accumulation of IL-2R alpha chain-specific mRNA but neither c-myc nor cdc2 mRNA was expressed. The addition of 100 nM rIL-2 to T cells activated by phorbol dibutyrate was able to induce a proliferative response, and under these conditions tyrosine phosphorylation of the 97-kDa protein, the transient increase in p56lck kinase activity, and specific mRNA for IL-2R alpha chain, c-myc, and cdc2 were detected. Unstimulated G0 T cells responded to 100 nM rIL-2 in the same manner as phorbol dibutyrate-activated cells. Irrespective of the signal-transducing structures involved, the IL-2-induced proliferative response closely correlates with an increase in p56lck kinase activity along with the tyrosine phosphorylation of a 97-kDa protein.
Kim
Y H
YH
Clinical Immunology Section, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Buchholz
M J
MJ
Nordin
A A
AA
D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D016259:Genes, myc / Q000187:drug effects; D019833:Genistein; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D007376:Interleukin-2; D007529:Isoflavones; D010750:Phosphoproteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013936:Thymidine