Tyrosine phosphorylation of a 100-kDa protein is correlated with cytotoxic T-lymphocyte function. Evidence from cis unsaturated fatty acid and phenylarsineoxide inhibition.
Cis unsaturated but not saturated fatty acids (FA) have been shown to specifically inhibit certain early responses in cytotoxic T-lymphocytes (CTL) including the rise in intracellular calcium, degranulation, and lethal hit delivery. They do not, however, affect other early events such as the turnover of phosphatidylinositol, T-cell receptor recognition, and CTL-cognate target cell conjugation. Antigen stimulation of CTL results in an increase in the tyrosine phosphorylation levels of more than 10 substrates. We now find that cis unsaturated but not saturated FA specifically inhibit antigen-stimulated tyrosine phosphorylation of only a single substrate, a 100-kDa protein (pp100). The characteristics of cis FA inhibition of the tyrosine phosphorylation of pp100 are virtually identical to the cis FA inhibition of the CTL functional responses. Inhibition occurs within seconds of cis FA addition, can be reversed by extracting the unesterified FA with albumin, can be initiated after stimulation, and has the same dose and FA molecular species dependence as the inhibition of the CTL responses. In addition, low concentrations of phenylarsine oxide specifically inhibit the tyrosine phosphorylation of pp100 and the CTL responses, but have no effect on other tyrosine phosphorylation events. These striking correlations suggest that pp100 may be central to specific early signaling events including lethal hit delivery and its tyrosine phosphorylation may be regulated by a plasma membrane protein tyrosine phosphatase.
Anel
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Division of Membrane Biology, Medical Biology Institute, La Jolla, California 92037.
Kleinfeld
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AM
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003720:Densitometry; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015151:Immunoblotting; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D001152:Arsenicals; D005231:Fatty Acids, Unsaturated; C029341:oxophenylarsine; D014443:Tyrosine; D000242:Cyclic AMP; D017027:Protein Tyrosine Phosphatases