Identification of distinct populations of PI-3 kinase activity following T-cell activation.
Activation of mature CD4+ T lymphocytes by antigen-presenting cells involves engagement of the CD3/T-cell antigen receptor complex along with the CD4 surface glycoprotein and the phosphorylation of cellular proteins on tyrosine residues leading to stimulation of a variety of cellular second-messenger systems. Several recent studies have implicated non-receptor protein tyrosine kinase of the src family, especially p56lck and p59fyn, in mediating at least a portion of these tyrosine phosphorylation events. In the present study we have examined the involvement of one type of second-messenger system, phosphatidylinositol-3 kinase (PI-3 kinase), in signal transduction during antibody-induced activation of normal resting human CD4+ T cells. We demonstrate that PI-3 kinase activity is increased following co-approximation of CD4 with the T-cell receptor and that PI-3 kinase activity co-precipitates with the CD4-p56lck complex. We also show that following T-cell activation a complex containing PI-3 kinase activity can be demonstrated in CD3 epsilon immunoprecipitates which is distinct from that which interacts with p56lck.
Thompson
P A
PA
Laboratory of Tumor Virus Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Gutkind
J S
JS
Robbins
K C
KC
Ledbetter
J A
JA
Bolen
J B
JB
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D019000:Phosphotyrosine; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019061:src-Family Kinases
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D019061:src-Family Kinases