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.
Laboratory of Tumor Virus Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
P A
PA
Thompson
J S
JS
Gutkind
K C
KC
Robbins
J A
JA
Ledbetter
J B
JB
Bolen
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