CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase.
T lymphocyte activation requires recognition of antigen by the antigen specific TCR as well as second co-stimulatory signals. This recognition event results in the activation of non-TCR linked protein tyrosine kinases (PTKs). The mechanism of co-stimulation of T cells is unknown except for the involvement of PTKs. The T cell surface molecule CD28 is effective in delivering co-stimulatory signals and prevents T cell anergy by inducing T cell proliferation in TCR stimulated T cells, primarily due to an increase in IL-2 production. The mechanism by which CD28 mediates this effect is currently unknown. Some conventional receptor molecules possess intrinsic tyrosine kinase and as a consequence of cross-linking or ligand binding, phosphorylate numerous tyrosines within their cytoplasmic tail, leading these tyrosines to become 'activated' and bind cytoplasmic effector molecules possessing Src homology 2 domains which specifically recognize phosphorylated tyrosines. One such cytoplasmic effector molecule is the phosphatidylinositol-3-phosphate kinase (PI3 kinase) which recognizes the motif phosphotyrosine-methione/valine-X-methionine (X being any amino acid) within the cytoplasmic tails of numerous receptor tyrosine kinases. As CD28 contains a copy of the PI3 kinase binding motif within its cytoplasmic tail, we investigated CD28 signaling and PI3 kinase activation. Here we demonstrate using the Jurkat cell line that CD28 becomes tyrosine phosphorylated following CD28 cross-linking and associates with PI3 kinase. Furthermore, a synthetic peptide representing the YM/VXM motif within the cytoplasmic tail of CD28 also interacts with PI3 kinase only when the tyrosine is phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)
August
A
A
Immunology Program, Sloan-Kettering Institute for Cancer Research, New York City, NY 10021.
Dupont
B
B
D000595:Amino Acid Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D014407:Tumor Cells, Cultured; D014443:Tyrosine
D018106:CD28 Antigens; D009842:Oligopeptides; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)