In vivo association between p56lck and MAP kinase during IL-2-mediated lymphocyte proliferation.
We previously reported that p56lck expression is upregulated in human B lymphocytes upon mitogenic stimulation. In this report, we characterized the molecules associated with p56lck in vivo in leukemic B cells costimulated with anti-mu Ab and IL-2 for 72 h. In vitro phosphorylation after p56lck immunoprecipitation indicated that p56lck is associated in vivo with the beta chain of the IL-2 receptor and p42 MAP kinase as well as a number of other proteins. Moreover, p56lck-associated MAP kinase is tyrosine and threonine phosphorylated, suggesting that it is activated. Prevention of DNA synthesis with aphidicolin abrogated this molecular association, and furthermore, cell cycle analysis with IL-2-dependent T cells showed that in cells in G1, MAP kinase was not associated to p56lck, whereas this p56lck-MAP kinase association was observed when cells are in S phase. Thus, p56lck and MAP kinase are only associated during S phase. These data suggest that MAP kinase in association with p56lck is directly involved in the control of IL-2-mediated DNA synthesis of both B and T lymphocytes.
D016590:Aphidicolin / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D016196:S Phase; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000032:analysis*
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D016590:Aphidicolin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1