Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.

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Abstract
Tumor necrosis factor .alpha. (TNF-.alpha.) stimulated the phosphorylation of a 28-kDa protein (p28) in the ME-180 line of human cervical carcinoma cells. The effect of TNF-.alpha. on the phosphorylation state of p28 was rapid (4-fold increase within 15 min) and persistent, remaining above the basal level for at least 2 hr. The specific binding of 125I-labeled TNF-.alpha. to cell-surface binding sites, the stimulation of p28 phosphorylation by TNF-.alpha., and the inhibition of cell proliferation by TNF-.alpha. occurred with nearly identical dose-response relationships. Two-dimensional SDS/PAGE resolved p28 into two isoforms having pI values of 6.2 and 6.1. A phosphorylated cap-binding protein was substantially enriched from lysates of control or TNF-.alpha.-treated ME-180 cells by affinity chromatography with 7-methylguanosine 5''-triphosphate-Sepharose. The phosphoprotein recovered from this procedure was the substrate for TNF-.alpha.-promoted phosphorylation, p28. Thus, TNF-.alpha. stimulates the phosphorylation of this mRNA cap-binding protein, which may be invovled in the transduction of TNF-.alpha.-receptor binding into cellular responses.