TY - JOUR
T1 - CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase
AU - August, Avery
AU - Dupont, Bo
N1 - Funding Information:
We thank Dr K. 0. Lloyd (SKI) for the use of his facilities for thin layer chromatography. This work was supported by the National Institutes of Health (CA-22507 and CA-08748).
PY - 1994/5
Y1 - 1994/5
N2 - T lymphocyte activation requires recognition of antigen by the antigen specific TCR as well as second co-stlmulatory signals. This recognition event results in the activation of non-TCR linked protein tyroslne klnases (PTKs). The mechanism of co-stlmulatlon of T cells is unknown except for the involvement of PTKs. The T cell surface molecule CD28 Is effective in delivering co-stlmulatory 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 tyroslne kinase and as a consequence of cross-linking or llgand binding, phosphorylate numerous tyroslnes within their cytoplasmlc tall, leading these tyroslnes to become 'activated' and bind cytoplasmlc effector molecules possessing Src homology 2 domains which specifically recognize phosphorylated tyroslnes. One such cytoplasmlc effector molecule is the phosphattdyllnosltol-3-phosphate kinase (PI3 kinase) which recognizes the motif phosphotyroslne - methlone/vallne - X - methlonlne (X being any amlno acid) within the cytoplasmlc tails of numerous receptor tyroslne klnases. As CD28 contains a copy of the PI3 kinase binding motif within its cytoplasmlc tail, we investigated CD28 signaling and PI3 kinase activation. Here we demonstrate using the Jurkat cell line that CD28 becomes tyroslne phosphorylated following CD28 cross-linking and associates with PI3 kinase. Furthermore, a synthetic peptlde representing the YM/VXM motif within the cytoplasmlc tall of CD28 also interacts with PI3 kinase only when the tyroslne is phosphorylated. CD28 co-stimulation, therefore, similar to that of CD19 and 'co-stlmulatlon' of B cells travel in part via the activation of the PI3 kinase pathway.
AB - T lymphocyte activation requires recognition of antigen by the antigen specific TCR as well as second co-stlmulatory signals. This recognition event results in the activation of non-TCR linked protein tyroslne klnases (PTKs). The mechanism of co-stlmulatlon of T cells is unknown except for the involvement of PTKs. The T cell surface molecule CD28 Is effective in delivering co-stlmulatory 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 tyroslne kinase and as a consequence of cross-linking or llgand binding, phosphorylate numerous tyroslnes within their cytoplasmlc tall, leading these tyroslnes to become 'activated' and bind cytoplasmlc effector molecules possessing Src homology 2 domains which specifically recognize phosphorylated tyroslnes. One such cytoplasmlc effector molecule is the phosphattdyllnosltol-3-phosphate kinase (PI3 kinase) which recognizes the motif phosphotyroslne - methlone/vallne - X - methlonlne (X being any amlno acid) within the cytoplasmlc tails of numerous receptor tyroslne klnases. As CD28 contains a copy of the PI3 kinase binding motif within its cytoplasmlc tail, we investigated CD28 signaling and PI3 kinase activation. Here we demonstrate using the Jurkat cell line that CD28 becomes tyroslne phosphorylated following CD28 cross-linking and associates with PI3 kinase. Furthermore, a synthetic peptlde representing the YM/VXM motif within the cytoplasmlc tall of CD28 also interacts with PI3 kinase only when the tyroslne is phosphorylated. CD28 co-stimulation, therefore, similar to that of CD19 and 'co-stlmulatlon' of B cells travel in part via the activation of the PI3 kinase pathway.
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U2 - 10.1093/intimm/6.5.769
DO - 10.1093/intimm/6.5.769
M3 - Article
C2 - 8080844
AN - SCOPUS:0028342859
SN - 0953-8178
VL - 6
SP - 769
EP - 774
JO - International immunology
JF - International immunology
IS - 5
ER -