The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions.
Pathogenic Yersinia resist uptake by eukaryotic cells by a mechanism involving the virulence protein YopH, a protein tyrosine phosphatase. We show that p130Cas and FAK are phosphorylated and recruited to peripheral focal complexes during bacterial uptake in HeLa cells. The inactive form of YopH interacts with the tyrosine phosphorylated forms of FAK and p130Cas and co-localizes with these proteins in focal adhesions. On the other hand, the presence of active YopH results in inhibition of uptake, dephosphorylation of p130Cas and FAK, and disruption of peripheral focal complexes. We suggest that p130Cas and FAK are substrates for YopH and that the dephosphorylation of these proteins impairs the uptake of Yersinia pseudotuberculosis into HeLa cells.
Persson
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C
Department of Cell and Molecular Biology, Umeå University, Sweden.
Carballeira
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N
Wolf-Watz
H
H
Fällman
M
M
D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins; D011972:Receptor, Insulin / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine / Q000378:metabolism*; D015011:Yersinia pseudotuberculosis / Q000201:enzymology / Q000378:metabolism*
C493841:BCAR1 protein, human; D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D019012:Integrin beta1; D010750:Phosphoproteins; D011506:Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia