Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition

Garton, Andrew J.; Burnham, Mary Rose; Bouton, Amy H.; Tonks, Nicholas K.

doi:10.1038/sj.onc.1201279

Cited by 150 publications

(122 citation statements)

References 31 publications

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“…CD2BP1 also independently binds a second intracellular ligand, the tyrosine phosphatase PTP-PEST, at a site separate from CD2. Because PTP-PEST dephosphorylates p130 cas , it is probable that focal adhesion can be readily down-modulated by this means (30,53). Transfection analysis in COS cells and Jurkat cells vis-à-vis CD2-dependent adhesion function are consistent with this view (20).…”

Section: Discussionmentioning

confidence: 64%

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

Tibaldi

Salgia

Reinherz

2002

Proc. Natl. Acad. Sci. U.S.A.

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Dynamic binding between CD2 and CD58 counter-receptors on opposing cells optimizes immune recognition through stabilization of cell-cell contact and juxtaposition of surface membranes at a distance suitable for T cell receptor-ligand interaction. Digitized time-lapse differential interference contrast and immunofluorescence microscopy on living cells now show that this binding also induces T cell polarization. Moreover, CD2 can facilitate motility of T cells along antigen-presenting cells via a movement referred to as scanning. Both activated CD4 and CD8 T cells are able to scan antigen-presenting cells surfaces in the absence of cognate antigen. Scanning is critically dependent on T cell ␤-integrin function, as well as myosin light chain kinase. More importantly, surface CD2 molecules rapidly redistribute on interaction with a cellular substratum, resulting in a 100-fold greater CD2 density in the uropod versus the leading edge. In contrast, no redistribution is observed for CD11a͞CD18 or CD45. Molecular compartmentalization of CD2, T cell receptor, and lipid rafts within the uropod prearranges the cellular activation machinery for subsequent immune recognition. This ''presynapse'' formation on primed T cells will likely facilitate the antigen-dependent recognition capability required for efficient immune surveillance.A rrival of antigen-laden dendritic cells into the lymph node results in the activation of naive T cells, leading to their proliferation and acquisition of effector functions (1). The subsequent migration of activated T cells into pathogen-invaded body tissues is a key feature of immunity and immune surveillance. Diapedesis of T cells through the vascular endothelium, as well as their crawling movement on the surface of antigen presenting cells (APCs), parenchymal cells and extracellular matrix (ECM), requires T cell polarization (2). Although the molecular basis of this process is not well understood, certain features have been identified. Cell polarization is characterized by the formation of a leading edge at the front of the cell and a uropod at its back, allowing conversion of mechanical forces generated through adhesion to a substratum into net cellular locomotion (3). While the actin cytoskeleton redistributes at the leading edge, the microtubule organizing center (MTOC) localizes within the uropod allowing a greater deformability of the migrating cells (4-6). Given that the MTOC and the Golgi apparatus colocalize, the secretion of soluble mediators is directed toward the ligated cell surface (7). Moreover, chemokine receptors responsible for the directionality of the migration along a gradient of chemoattractants are concentrated within the leading edge (8). In contrast, the uropod mediates important adhesion functions, as suggested by accumulation of a notable number of adhesion molecules including ICAM-1, CD44, CD43, P-selective glycoprotein ligand 1 (PSGL-1), and L-selectin during migration (9, 10). The uropod therefore appears to anchor the cell to the ECM, APCs, or endothelial cells w...

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Section: Discussionmentioning

confidence: 64%

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

Tibaldi

Salgia

Reinherz

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In a screen for substrates of tyrosine phosphatase PTP-PEST using a substratetrapping approach, Garton et al (1996) identified that p130 Cas can interact with catalytically inactive PTP-PEST (Garton et al 1996). However, it was later discovered, through a more careful mapping experiment, that the major interaction domain between p130 Cas and wild-type PTP-PEST is at the SH3 domain of p130 Cas (Garton et al 1997). Similarly, over-expression of PTP1B, another abundant intracellular tyrosine phosphatase, has been shown to interact with p130 Cas through its SH3 domain (Liu et al 1996).…”

Section: Discussionmentioning

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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“…Cas , Hef1/Cas-L, Sin/Efs, and Csk (2)(3)(4)(5). In addition, a novel and non-classical polyproline region in PTP-PEST has been implicated in the binding of paxillin and Hic-5 (6 -9).…”

mentioning

confidence: 99%

“…The identification of p130 Cas as a substrate of PTP-PEST using catalytically inactive substrate trapping mutants of the enzyme was a major step in the elucidation of some of the biological functions of this protein (3,5,12). Although the PTP domain of PTP-PEST is sufficient to recognize the p130 Cas phosphorylated on tyrosine residues in vitro, an additional level of specificity is mediated via a SH3 domain-dependent association in vivo (3,5).…”

mentioning

confidence: 99%

PSTPIP Is a Substrate of PTP-PEST and Serves as a Scaffold Guiding PTP-PEST Toward a Specific Dephosphorylation of WASP

Côté¹,

Chung²,

Théberge³

et al. 2002

Journal of Biological Chemistry

116

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PSTPIP is a tyrosine-phosphorylated protein involved in the organization of the cytoskeleton. Its ectopic expression induces filipodial-like membrane extensions in NIH 3T3 cells. We previously observed a defect in cytokinesis and an increase in the tyrosine phosphorylation of PSTPIP in PTP-PEST-deficient fibroblasts. In this article, we demonstrate that PTP-PEST and PSTPIP are found in the same complexes in vivo and that they interact directly through the CTH domain of PTP-PEST and the coiled-coil domain of PSTPIP. We tested pathways that could regulate the tyrosine phosphorylation of PSTPIP. We found that the activation of the epidermal growth factor and platelet-derived growth factor receptors can induce PSTPIP phosphorylation. With the use of the PP2 inhibitor, we demonstrate that Src kinases are not involved in the epidermal growth factor-mediated phosphorylation of PSTPIP. Together with previous results, this suggests that c-Abl is the critical tyrosine kinase downstream of growth factor receptors responsible for PSTPIP phosphorylation. We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. This is an important finding since tyrosine 367 of PSTPIP was also proposed as a candidate phosphorylation site involved in the negative regulation of the association between PSTPIP and WASP. In this respect, we observed that the PSTPIP⅐ WASP complex is stable in vivo and is not affected by the phosphorylation of PSTPIP. Furthermore, we demonstrate that PSTPIP serves as a scaffold protein between PTP-PEST and WASP and allows PTP-PEST to dephosphorylate WASP. This finding suggests a possible mechanism for PTP-PEST to directly modulate actin remodeling through the PSTPIP-WASP interaction.

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Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition

Cited by 150 publications

References 31 publications

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

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

PSTPIP Is a Substrate of PTP-PEST and Serves as a Scaffold Guiding PTP-PEST Toward a Specific Dephosphorylation of WASP

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Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition

Cited by 150 publications

References 31 publications

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance

Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas

PSTPIP Is a Substrate of PTP-PEST and Serves as a Scaffold Guiding PTP-PEST Toward a Specific Dephosphorylation of WASP

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