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

Bacterially encoded proteins are known to affect eukaryotic signalling pathways and thus cell growth and differentiation. The enteric pathogen Yersinia pseudotuberculosis (YP) can translocate Yersinia outer proteins (Yops) into eukaryotic cells. Recently, MKK proteins have been identified as tentative targets of YopJ-mediated inhibition of ligand receptor-dependent signal transduction in mammalian cells. These results prompted us to assess whether multiple signal transduction pathways and their downstream target genes would also be subject to regulation by YopJ. Here, we show that YopJ effectively blocks the lipopolysaccharide (LPS) receptor, the interleukin (IL)-1 beta receptor and the UVC-induced activation of the transcription receptor cAMP response element-binding protein (CREB). In addition, by abrogating the phosphorylation of CREB and thus activating protein (AP)-1-dependent transcription, YopJ can block LPS-induced clonal expansion that is associated with an adaptive immune response. Thus, YopJ interferes with multiple pathways converging on the transcription factor CREB. Our data are discussed in the context of YopJ acting as an antagonist to circumvent innate and adaptive immune responses at multiple levels.