TYROSINE PHOSPHORYLATION OF A 100-KDA PROTEIN IS CORRELATED WITH CYTOTOXIC T-LYMPHOCYTE FUNCTION - EVIDENCE FROM CIS-UNSATURATED FATTY-ACIDAND PHENYLARSINEOXIDE INHIBITION

Cis unsaturated but not saturated fatty acids (FA) have been shown to specifically inhibit certain early responses in cytotoxic T-lymphocyte s (CTL) including the rise in intracellular calcium, degranulation, an d lethal hit delivery. They do not, however, affect other early events such as the turnover of phosphatidylinositol, T-cell receptor recogni tion, and CTL-cognate target cell conjugation. Antigen stimulation of CTL results in an increase in the tyrosine phosphorylation levels of m ore than 10 substrates. We now find that cis unsaturated but not satur ated FA specifically inhibit antigen-stimulated tyrosine phosphorylati on of only a single substrate, a 100-kDa protein (pp100). The characte ristics 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 b e reversed by extracting the unesterified FA with albumin, can be init iated after stimulation, and has the same dose and FA molecular specie s 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 su ggest that pp100 may be central to specific early signaling events inc luding lethal hit delivery and its tyrosine phosphorylation may be reg ulated by a plasma membrane protein tyrosine phosphatase.