SHIGELLA-FLEXNERI HELA-CELL INTERACTIONS - A PUTATIVE ROLE FOR HOST-CELL PROTEIN-KINASES

Epithelial cell invasion has been shown to be a prerequisite for Shige lla flexneri virulence. Recently, we have documented the induction of transcription factor DNA binding activities as a result of S. flexneri challenge of HeLa cells. In this report, we show that HeLa cells chal lenged with S. flexneri display differences in phosphotyrosine-contain ing proteins. These changes are detected as early as 5 min post-challe nge. Challenge with a noninvasive ipaB mutant strain resulted in the i nduction of a similar, but less intense, profile of phosphotyrosine-co ntaining host cell proteins. Phosphotyrosine-containing proteins could be detected in S. flexneri, but were unique from those detected follo wing HeLa cell challenge. S. flexneri invasion of HeLa cell monolayers was reduced by treatment with protein kinase inhibitors. These data s uggest a role for protein kinases in the initial response of host cell s to S. flexneri.