Interaction between the Yersinia tyrosine phosphatase YopH and its macrophage substrate, Fyn-binding protein, Fyb.
Pathogenic Yersinia species can evade phagocytosis by injecting virulence effectors that interfere with the phagocytic machinery of host cells. One of these virulence effectors is the protein tyrosine phosphatase YopH. Through its enzymatic activity, YopH interferes with the initial phagocytic process by affecting signalling for cytoskeletal rearrangements. Fyb (Fyn-binding protein), which is an immune cell-specific adaptor protein, has been identified as a substrate of YopH in macrophages. In this study, the interaction between YopH and Fyb is studied. We show that YopH binds to Fyb via different regions in both phosphotyrosine-dependent and phosphotyrosine-independent ways. The phosphotyrosine substrate binding N-terminal part (1-130) of YopH as well as the C-terminal catalytic region binds to Fyb in a phosphotyrosine-dependent manner. We also show that a central part of YopH (130-260) interacts with the Fyb C-terminus (548-783) in a phosphotyrosine-independent manner. Further, we demonstrate that the N-terminal binding region of YopH is important for YopH-mediated functions on macrophages such as dephosphorylation of Fyb, blockage of phagocytosis, and cytotoxic effects.
Yuan
Ming
M
Department of Molecular Biology, Umeå University, Umeå, Sweden.
Deleuil
Fabienne
F
Fällman
Maria
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D047468:Immunoprecipitation; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D015007:Yersinia / Q000201:enzymology* / Q000472:pathogenicity
D048868:Adaptor Proteins, Signal Transducing; D001425:Bacterial Outer Membrane Proteins; C106957:FYB1 protein, human; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia