Free Content The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated signalling complex in macrophages

Authors: Black, Deborah S.1; Marie-Cardine, Anne2; Schraven, Burkhart2; Bliska, James B.1

Source: Cellular Microbiology, Volume 2, Number 5, October 2000 , pp. 401-414(14)

Publisher: Blackwell Publishing

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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.

Document Type: Research article

DOI: 10.1046/j.1462-5822.2000.00061.x

Affiliations: 1: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA. 2: Ruprecht-Karls University of Heidelberg, Institute for Immunology, 69120 Heidelberg, Germany.

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