Phorbol ester treatment inhibits phosphatidylinositol 3-kinase activation by, and association with, CD28, a T-lymphocyte surface receptor

Jill E. Hutchcroft, David P. Franklin, Betsy Tsai, Dee Harrison-Findik, Lyuba Varticovski, Barbara E. Bierer

Research output: Contribution to journalArticle

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Abstract

CD28 is a costimulatory receptor found on the surface of most T lymphocytes. Engagement of CD28 induces interleukin 2 (IL-2) production and cell proliferation when combined with an additional signal such as treatment with phorbol ester, an activator of protein kinase C. Recent studies hove established that after CD28 ligation, the cytoplasmic domain of CD28 can bind to the 85-kDa subunit of phosphatidylinositol 3-kinase (PI3 kinase). There is a concomitant increase in PI3 lipid kinase activity that may be important in CD28 signaling. Despite the requirement of phorbol 12-myristate 13-acetate (PMA) for effector function, we have found, however, that treatment of Jurkat T cells with the phorbol ester PMA dramatically inhibits (i) the association of PI3 kinase with CD28, (ii) the ability of p85 PI3 kinase to be immunoprecipitated by anti-phosphotyrosine antibodies, and (iii) the induction of PI3 kinase activity after stimulation of the cells with the anti-CD28 monoclonal antibody 9.3. These changes occur within minutes of PMA treatment and are persistent. In addition, we have found that wortmannin, a potent inhibitor of PI3 kinase, does not interfere with the induction of IL- 2 after stimulation of Jurkat T cells with anti-CD28 monoclonal antibody and PMA. We conclude that PI3 kinase activity may not be required for CD28- dependent IL-2 production from Jurkat T cells in the presence of PMA.

Original languageEnglish (US)
Pages (from-to)8808-8812
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number19
DOIs
StatePublished - Sep 12 1995

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Phosphatidylinositol 3-Kinase
Phorbol Esters
Acetates
T-Lymphocytes
Jurkat Cells
Interleukin-2
Monoclonal Antibodies
Phosphotyrosine
Phosphatidylinositol 3-Kinases
Protein Kinase C
Ligation
Anti-Idiotypic Antibodies
Cell Proliferation
phorbol-12-myristate
Lipids

ASJC Scopus subject areas

  • General

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Phorbol ester treatment inhibits phosphatidylinositol 3-kinase activation by, and association with, CD28, a T-lymphocyte surface receptor. / Hutchcroft, Jill E.; Franklin, David P.; Tsai, Betsy; Harrison-Findik, Dee; Varticovski, Lyuba; Bierer, Barbara E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 19, 12.09.1995, p. 8808-8812.

Research output: Contribution to journalArticle

Hutchcroft, Jill E. ; Franklin, David P. ; Tsai, Betsy ; Harrison-Findik, Dee ; Varticovski, Lyuba ; Bierer, Barbara E. / Phorbol ester treatment inhibits phosphatidylinositol 3-kinase activation by, and association with, CD28, a T-lymphocyte surface receptor. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 19. pp. 8808-8812.
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