The bacterial protein YopJ abrogates multiple signal transduction pathwaysthat converge on the transcription factor CREB

Bacterially encoded proteins are known to affect eukaryotic signalling path ways and thus cell growth and differentiation. The enteric pathogen Yersini a pseudotuberculosis (YP) can translocate Yersinia outer proteins (Yops) in to eukaryotic cells. Recently, MKK proteins have been identified as tentati ve targets of YopJ-mediated inhibition of ligand receptor-dependent signal transduction in mammalian cells. These results prompted us to assess whethe r multiple signal transduction pathways and their downstream target genes w ould also be subject to regulation by YopJ. Here, we show that YopJ effecti vely blocks the lipopolysaccharide (LPS) receptor, the interleukin (IL)-1 b eta receptor and the UVC-induced activation of the transcription receptor c AMP response element-binding protein (CREB). In addition, by abrogating the phosphorylation of CREB and thus activating protein (AP)-1-dependent trans cription, YopJ can block LPS-induced clonal expansion that is associated wi th an adaptive immune response. Thus, YopJ interferes with multiple pathway s converging on the transcription factor CREB. Our data are discussed in th e context of YopJ acting as an antagonist to circumvent innate and adaptive immune responses at multiple levels.