Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol 3-kinase in Jurkat T cells.

The T cell surface molecule CD28 can provide costimulatory signals that permit the full activation of T cells. Here we demonstrate that stimulation of CD28, either by B7, its natural ligand, or by the anti-CD28 monoclonal antibody 9.3, induces an association between CD28 and phosphatidylinositol 3-kinase (PI3-K) in Jurkat T ...
cells, raising the possibility that an interaction with PI3-K contributes to CD28-mediated signaling. To examine the mechanism of the association, we synthesized tyrosine-phosphorylated oligopeptides corresponding to each of the four tyrosines in the CD28 cytoplasmic domain. When added to lysates of B7-stimulated Jurkat cells, the oligopeptide corresponding to Tyr 173 inhibits the coimmunoprecipitation of PI3-K with CD28; the other oligopeptides have no effect. Tyr 173 is contained within the sequence YMNM, a motif that is also found in the platelet-derived growth factor receptor and that, when phosphorylated, forms a high affinity binding site for the p85 subunit of PI3-K. These observations suggest that phosphorylation of Tyr 173 may mediate the interaction between CD28 and PI3-K. However, because CD28 is not known to be phosphorylated, it remains possible that CD28 interacts with PI3-K through a mechanism independent of tyrosine phosphorylation.
Mesh Terms:
Animals, Antigens, CD, Base Sequence, CD28 Antigens, Cell Line, Humans, Kinetics, Mast-Cell Sarcoma, Mice, Molecular Sequence Data, Oligopeptides, Phosphatidylinositol 3-Kinases, Phosphopeptides, Phosphotransferases (Alcohol Group Acceptor), Phosphotyrosine, Protein Binding, Signal Transduction, T-Lymphocytes, Transfection, Tumor Cells, Cultured, Tyrosine
J. Exp. Med.
Date: Mar. 01, 1994
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