The PTPase YopH inhibits uptake of<i>Yersinia</i>, tyrosine phosphorylation of p130<sup>Cas</sup>and FAK, and the associated accumulation of these proteins in peripheral focal adhesions

Persson, Cathrine; Carballeira, Nivia; Wolf‐Watz, Hans; Fällman, Maria

doi:10.1093/emboj/16.9.2307

Cited by 335 publications

(323 citation statements)

References 64 publications

(114 reference statements)

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“…Our data suggest that at least one of these proteins is FAK. Interestingly, Yersinia inhibits phagocytosis by translocation of YopH, a protein tyrosine phosphatase (PTP) that mediates FAK dephosphorylation (Persson et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

et al. 2002

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SummaryEnteropathogenic Escherichia coli (EPEC) is a human-specific pathogen that causes severe diarrhoea in young children. The disease involves intimate interaction between the pathogen and the brush border of enterocytes. During infection, EPEC uses a type III secretion system (TTSS) to inject several proteins into the infected cells, and these effector proteins modify specific processes in the host cell. We show that, upon infection, EPEC induces detachment of the infected host cells from the substratum, modification of focal adhesions (FA) in the infected cells and specific dephosphorylation of focal adhesion kinase (FAK). We also show that EPEC-induced cell detachment is dependent on FAK expression by the infected cells. Finally, we demonstrate that cell detachment, FA modification and FAK dephosphorylation are dependent on functional TTSS in the infecting EPEC. These results suggest that EPEC is using its TTSS to inject protein(s) into the infected cells, which can induce FAK dephosphorylation, as well as FAK-dependent FA modification and cell detachment. These processes are specific and probably play an important role in EPEC virulence.

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Section: Discussionmentioning

confidence: 99%

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

et al. 2002

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“…Interestingly, YopH, a protein tyrosine phosphatase that is translocated into mammalian cells by pathological bacteria Yersiniae, can also cause dephosphorylation of p130 Cas (Black & Bliska 1997;Persson et al 1997). A catalytically inactive mutant of YopH was shown to be localized to focal adhesions.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, several cytosolic forms of the PTPs have been found to bind and/or dephosphorylate key components of various signalling pathways (Sun et al 1993;Feng & Pawson 1994;Liu et al 1996;Tonks & Neel 1996;Barford & Neel 1998;Shen et al 1998;Tamura et al 1998). p130 Cas itself has been shown to be regulated by several cytosolic PTPs (Black & Bliska 1997;Garton et al 1996;Persson et al 1997;Liu et al 1998). LAR belongs to a family of transmembrane receptor-like protein tyrosine phosphatases and is a prototype of three closely related but differentially expressed subfamily members (Streuli et al 1988;Krueger et al 1990;Yu et al 1992;Katsura et al 1995;Pulido et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130^Cas

Weng

Wang

1999

Genes to Cells

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Background: LAR is a transmembrane receptor-like protein tyrosine phosphatase (PTP). Genetic studies of Drosophila LAR suggest that LAR may function to regulate cell adhesions or adhesion-mediated signal transduction. The over-expression of LAR in mammalian tissue culture cells does not affect cell adhesion but induces caspase-dependent apoptosis. This study investigates molecular mechanisms of LAR-induced apoptosis by searching for in vivo substrates of LAR which are responsible for LAR-induced apoptosis.

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“…YopH dephosphorylates p130Cas, focal adhesion kinase (FAK), paxillin and the Fyn-binding protein (FBP), thereby inhibiting the formation of focal adhesion complexes ( Fig. 1) (Black and Bliska, 1997;Persson et al, 1997;Black et al, 1998;Hamid et al, 1999). YopH bears a similar three-dimensional structure to the mammalian PTPases (Stuckey et al, 1994), suggesting that YopH most probably catalyses tyrosine phosphate hydrolysis via a similar mechanism to the mammalian PTPases.…”

Section: Yophmentioning

confidence: 99%

Yersinia effectors target mammalian signalling pathways

2002

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SummaryAnimals have an immune system to fight off challenges from both viruses and bacteria. The first line of defence is innate immunity, which is composed of cells that engulf pathogens as well as cells that release potent signalling molecules to activate an inflammatory response and the adaptive immune system. Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure survival in the host. Yersinia spp. use a type III secretion system to translocate these effector proteins, called Yops, into the host. This report outlines how Yops thwart the signalling machinery of the host immune system. Introduction Innate immunity and signallingInnate immunity is the first line of defence against bacterial and viral infection (for a review of innate immunity, see Medzhitov and Janeway, 2000). The cells involved in the immune response use a wide variety of signalling cascades to activate processes such as phagocytosis, cytokine production and release and production of reactive oxygen species. In addition to eliminating pathogens, the innate immune system activates the adaptive immune response through the presentation of foreign peptides to T cells.Phagocytosis is an essential component of the innate immune system (May and Machesky, 2001). Rearrangement of the actin cytoskeleton during phagocytosis is mediated by the recruitment of proteins that function in actin rearrangement; these include paxillin, p130Cas and focal adhesion kinase (FAK) (Greenberg et al., 1990;Allen and Aderem, 1996). These proteins may form through M cells (microfold cells), which are specialized cells that take up foreign antigens, in intestinal Peyer's patches (Autenrieth and Firsching, 1996). Recognition of Yersinia by M cells is mediated via b1 integrins on the M-cell plasma membrane and the invasin protein of Yersinia (Marra and Isberg, 1997;Clark et al., 1998). Once Yersinia has penetrated the M cells, it can localize in the lymphoid tissue of its host.The recently sequenced genome of Y. pestis (Parkhill et al., 2001) suggests that many of the genes that Yersinia uses during infection and invasion, including adhesins, secretion systems and insecticidal toxins, have been acquired from other bacteria and viruses. Furthermore, all three pathogenic species of Yersinia harbour an extrachromosomal plasmid of 70 kb that is essential for virulence (Portnoy and Martinez, 1985). This plasmid contains the genes of a type III secretion system, a translocation apparatus highly conserved among pathogenic Gram-negative bacteria (for a review, see Cornelis, 1998). This secretion system is responsible for the translocation of the Yersinia effectors, termed Yops, into the host cell. Once inside the host cell, Yops carry out disruption of signalling cascades that activate the processes of phagocytosis, cytokine release and respiratory burst. Six Yop effectors have been identified (YopH, YopE, YopJ/P, YpkA/YopO, YopT and YopM). Some of these effectors are known to function in the downregulation of critical signalling cascades of the immune system (Fig...

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The PTPase YopH inhibits uptake ofYersinia, tyrosine phosphorylation of p130^Casand FAK, and the associated accumulation of these proteins in peripheral focal adhesions

Cited by 335 publications

References 64 publications

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130^Cas

Yersinia effectors target mammalian signalling pathways

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The PTPase YopH inhibits uptake ofYersinia, tyrosine phosphorylation of p130Casand FAK, and the associated accumulation of these proteins in peripheral focal adhesions

Cited by 335 publications

References 64 publications

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

Enteropathogenic Escherichia coli induces modification of the focal adhesions of infected host cells

Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas

Yersinia effectors target mammalian signalling pathways

Contact Info

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The PTPase YopH inhibits uptake ofYersinia, tyrosine phosphorylation of p130^Casand FAK, and the associated accumulation of these proteins in peripheral focal adhesions

Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130^Cas