Shigella flexneri-HeLa cell interactions: a putative role for host cell protein kinases.

Epithelial cell invasion has been shown to be a prerequisite for Shigella 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 challenged with S. flexneri display differences in phosphotyrosine-containing proteins. These changes are detected as early as 5 min post-challenge. Challenge with a noninvasive ipaB mutant strain resulted in the induction of a similar, but less intense, profile of phosphotyrosine-containing host cell proteins. Phosphotyrosine-containing proteins could be detected in S. flexneri, but were unique from those detected following HeLa cell challenge. S. flexneri invasion of HeLa cell monolayers was reduced by treatment with protein kinase inhibitors. These data suggest a role for protein kinases in the initial response of host cells to S. flexneri.