Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line.
Recently, interleukin 2 (IL-2) has been shown to induce increased activity of the p56lck protein-tyrosine kinase (PTK) in T-cell and natural killer cell lines, and evidence for a direct interaction between the p75 subunit of the IL-2 receptor (IL-2R) and this src-family kinase has been reported. Though these findings suggest a central role for lck in IL-2 signal transduction, one problem with this idea is that not all IL-2-responsive cells express the lck gene. For this reason, we examined the effects of IL-2 on the activity of src-like kinases in a pro-B cell line, F7, that lacks p56lck but that displays high-affinity IL-2Rs and vigorously proliferates in response to this lymphokine. Of the eight known src-family PTKs, F7 cells were shown to contain only p53/56lyn, p59fyn, and a small amount of p62yes. Stimulation of resting F7 cells with IL-2 induced a rapid (detectable within 1 min and maximal at 15 min) and concentration-dependent increase in the specific activity of p53/56lyn kinase, as assessed by in vitro kinase assays. This effect of IL-2 on p53/56lyn kinase was specific, since no IL-2-inducible changes were detected in the activities of the p59fyn and p62yes kinases. Furthermore, by using a monoclonal antibody specific for the approximately 75-kDa beta subunit of the IL-2R (referred to as p75/IL-2R beta), evidence for physical association between the lyn kinase and the IL-2R complex was obtained, in that a small proportion of the p53/56lyn kinase in F7 cells, but no detectable p59fyn kinase, was coimmunoprecipitated with p75/IL-2R beta. When combined with the recent evidence that IL-2 regulates p56lck in T cells, these results indicate that some flexibility exists in the ability of various src-like PTKs to participate in IL-2 signal transduction mechanisms and raise the possibility that lineage-specific (T-versus B-cell) responses to IL-2 may be determined at least in part by the repertoire of src-like PTKs expressed in the cell.
Torigoe
T
T
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Saragovi
H U
HU
Reed
J C
JC
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases