Author(s): Black DS, MarieCardine A, Schraven B, Bliska JB
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Abstract The Yersinia protein tyrosine phosphatase (PTP) YopH is translocated into eukaryotic cells by a type III secretion system that requires bacterial-host cell contact. YopH is composed of two modular effector domains: a substrate-binding domain located in the N-terminal region (residues 1-130) and a PTP catalytic domain located in the C-terminal region (residues 206-468). Previous studies have shown that YopH selectively targets tyrosine-phosphorylated proteins of approximate molecular weight 120 kDa (p120) and 55 kDa (p55) in murine macrophages. It has been demonstrated that p120 actually represents two tyrosine-phosphorylated target proteins, Cas and Fyb. We used the substrate-binding domain of YopH to affinity purify tyrosine-phosphorylated target proteins from lysates of J774A.1 macrophages. Protein microsequencing identified p55 as murine SKAP-HOM. Direct interaction between SKAP-HOM and a catalytically inactive form of YopH was demonstrated in vitro and in macrophages. In addition, we obtained evidence that SKAP-HOM is tyrosine phosphorylated in response to macrophage cell adhesion and that it forms a signalling complex with Fyb. We suggest that dephosphorylation of SKAP-HOM and Fyb by YopH allows yersiniae to interfere with a novel adhesion-regulated signal transduction pathway in macrophages.
This article was published in Cell Microbiol
and referenced in Journal of Clinical & Cellular Immunology