Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway.
Stimulation of T cells or the Jurkat T-cell line with soluble antibodies to the CD3/T-cell receptor complex causes mobilization of cytoplasmic Ca2+, which is blocked by pertussis toxin but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and translocation of protein kinase C activity from the cytoplasm to the membrane. Such stimulation also causes phosphorylation of pp60c-src at an amino-terminal serine residue. These activities are consistent with induction of phosphatidylinositol metabolism after antibody binding. Anti-CD3 stimulation with antibody in solution, however, does not cause Jurkat cells to release interleukin 2 and blocks rather than induces proliferation of T cells. Induction of interleukin 2 production by Jurkat cells and proliferation by normal T cells requires anti-CD3 stimulation with antibody on a solid support, such as Sepharose beads or a plastic dish. Thus, we examined phosphorylation of pp60c-src after stimulation of Jurkat cells with anti-CD3 in solution or on solid phase. Both of these caused serine phosphorylation of pp60c-src that was indistinguishable even after 4 h of stimulation. These results indicate that the mode of anti-CD3 stimulation (in solution or on solid phase) controls a cellular function that modifies the consequences of signal transduction through phosphatidylinositol turnover.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002451:Cell Compartmentation; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D010766:Phosphorylation; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src); D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D019000:Phosphotyrosine; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D011493:Protein Kinase C; D002118:Calcium