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Science 30 March 1990:
Vol. 247. no. 4950, pp. 1584 - 1587
DOI: 10.1126/science.2138816
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Articles

Science, Vol 247, Issue 4950, 1584-1587
Copyright © 1990 by American Association for the Advancement of Science

articles

T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation

T Mustelin, KM Coggeshall, N Isakov, and A Altman

Scripps Clinic and Research Foundation, Immunology Department/IMM3, La Jolla, CA 92037.

Triggering of the antigen-specific T cell receptor-CD3 complex (TCR-CD3) stimulates a rapid phospholipase C-mediated hydrolysis of inositol phospholipids, resulting in the production of second messengers and in T cell activation and proliferation. The role of tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited TPK activity and tyrosine phosphorylation of the TCR zeta subunit, but not phospholipase C activity, genistein prevented TCR-CD3-mediated phospholipase C activation, interleukin-2 receptor expression, and T cell proliferation. These findings indicate that tyrosine phosphorylation is an early and critical event that most likely precedes, and is a prerequisite for, inositol phospholipid breakdown during receptor-mediated T cell activation.


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