Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism.
The tyrosine phosphatase YopH is an essential virulence factor produced by pathogenic Yersinia species. YopH is translocated into host cells via a type III secretion system and its dephosphorylating activity causes disruption of focal complex structures and blockage of the phagocytic process. Among the host cell targets of YopH are the focal adhesion proteins Crk-associated substrate (p130Cas) and focal adhesion kinase (FAK) in epithelial cells, and p130Cas and Fyn-binding protein (Fyb) in macrophages. Previous studies have shown that the N-terminal domain of YopH acts as a substrate-binding domain. In this study, the mechanism and biological importance of the targeting of YopH to focal complexes relative to its interaction with p130Cas/Fyb was elucidated. Mutants of YopH that were defective in p130Cas/Fyb binding but otherwise indistinguishable from wild type were constructed. Mutants unable to bind p130Cas did not localize to focal complex structures in infected cells, indicating that the association with p130Cas is critical for appropriate subcellular localization of YopH. These yopH mutants were also clearly attenuated in virulence, showing that binding to p130Cas and/or Fyb is biologically relevant in Yersinia infections.
Deleuil
Fabienne
F
Department of Molecular Biology, Umeå University, Umeå, Sweden.
Mogemark
Lena
L
Francis
Matthew S
MS
Wolf-Watz
Hans
H
Fällman
Maria
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D050719:Crk-Associated Substrate Protein; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010587:Phagocytosis; D010750:Phosphoproteins / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000378:metabolism*; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology*
D048868:Adaptor Proteins, Signal Transducing; C493841:BCAR1 protein, human; D001425:Bacterial Outer Membrane Proteins; C493842:Bcar1 protein, mouse; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; C106957:FYB1 protein, human; C491468:Fyb protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia