Potent Stimulation of SH-PTP2 Phosphatase Activity by Simultaneous Occupancy of Both SH2 Domains

Pluskey, Scott; Wandless, Thomas J.; Walsh, Christopher T.; Shoelson, Steven E.

doi:10.1074/jbc.270.7.2897

Cited by 269 publications

(220 citation statements)

References 25 publications

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“…Overexpression of a catalytically compromised SHP-2 protein (Rivard et al, 1995) or microinjection of either a GST-fusion protein containing the SH2 domains of SHP-2 or neutralizing antibodies (Roche et al, 1996) inhibited PDGF-induced mitogenicity. It has previously been shown that Tyr1009 in the PDGF breceptor binds to SHP-2 (Kazlauskas et al, 1993), and that the association between the SH2 domains of SHP-2 and its target proteins triggers activation of the phosphatase activity of SHP-2 Pluskey et al, 1995). Simultaneous occupancy of both SH2 domains by phosphopeptides is required for full activation of the phosphatase activity of SHP-2 (Eck et al, 1996;Jackson et al, 1997;Ohnishi et al, 1996;Pluskey et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…It has previously been shown that Tyr1009 in the PDGF breceptor binds to SHP-2 (Kazlauskas et al, 1993), and that the association between the SH2 domains of SHP-2 and its target proteins triggers activation of the phosphatase activity of SHP-2 Pluskey et al, 1995). Simultaneous occupancy of both SH2 domains by phosphopeptides is required for full activation of the phosphatase activity of SHP-2 (Eck et al, 1996;Jackson et al, 1997;Ohnishi et al, 1996;Pluskey et al, 1995). This suggests that additional autophosphorylation sites in the PDGF b-receptor might contribute to the activation of SHP-2.…”

Section: Introductionmentioning

confidence: 99%

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SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis

et al. 1999

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Activation of the b-receptor for platelet-derived growth factor (PDGF) by its ligand leads to autophosphorylation on a number of tyrosine residues. Here we show that Tyr763 in the kinase insert region is a novel autophosphorylation site, which after phosphorylation binds the protein tyrosine phosphatase SHP-2. SHP-2 has also previously been shown to bind to phosphorylated Tyr1009 in the PDGF b-receptor. Porcine aortic endothelial (PAE) cells transfected with a PDGF breceptor in which Tyr763 and Tyr1009 were mutated to phenylalanine residues failed to associate with SHP-2 after ligand stimulation. Morover, PDGF-BB-induced Ras GTP-loading and Erk2 activation were severely compromised in the receptor mutant. Whereas the mitogenic response to PDGF-BB remained at the same level as in cells expressing wild-type PDGF b-receptor, chemotaxis induced by PDGF-BB was signi®cantly decreased in the case of the Y763F/Y1009F mutant cells, suggesting an important role for SHP-2 in chemotactic signaling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis

et al. 1999

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“…SHP-2 binds directly to growth factor receptors, such as those of platelet-derived growth factor receptor and epidermal growth factor (EGF) receptor, and undergoes tyrosine phosphorylation in response to receptor stimulation by ligand Vogel et al, 1993;Matozaki and Kasuga, 1996;Neel and Tonks, 1997). Furthermore, in response to insulin, SHP-2 binds via its SH2 domains to IRS-1, a major substrate for the insulin receptor tyrosine kinase (Sun et al, 1991) and is thereby activated (KuhneÂ et al, 1993;Matozaki et al, 1995;Pluskey et al, 1995). The expression of a catalytically inactive SHP-2 inhibits insulin-induced activation of RAS and mitogen-activated protein (MAP) kinase (Noguchi et al, 1994;Milarski and Saltiel, 1994;Xiao et al, 1994;Yamauchi et al, 1995) as well as EGF-induced MAP kinase activation (Bennett et al, 1996) and thereby blocks DNA synthesis and cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

et al. 1998

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SHPS-1 is an *120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 ®broblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not a ect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-de®cient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this e ect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.

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“…This enzyme binds to IRS-1 at a speci®c phosphotyrosine residue, and its catalytic activity is increased as a result of this interaction (Pluskey et al, 1995). We and others have previously shown that SHP2 is a required positive mediator of insulin/IGF-I signaling (Xiao et al, 1994;Yamauchi et al, 1995;Milarski and Saltiel, 1994).…”

Section: Microinjection Of Reagents Directed Against Irs-1 and Associmentioning

confidence: 98%

Prolonged vs transient roles for early cell cycle signaling components

Rose¹,

Xiao²,

Pillay

et al. 1998

Oncogene

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Both p21ras and phosphatidylinositol 3-kinase are critical elements in signaling pathways mediating insulin/IGF-I induced cell cycle progression. For example, microinjection of antibodies, peptides, or recombinant proteins which block the interaction of the SH2 domains of the PI 3-k p85a subunit with tyrosine phosphorylated intracellular targets blocks insulin mediated DNA synthesis. We report here that this inhibitory phenotype is observed whether the injections are made into quiescent cells (the standard approach), or at any time point during G 1 phase subsequent to stimulation. This observation is not true, however, for the major substrate of the insulin/ IGF-I receptor (IRS-1) despite the well known interaction of p85 with IRS-1. Antibodies to IRS-1 are inhibitory only when injected during the ®rst 15 min of G 1 phase, as are antibodies to another major IRS-1 binding protein, the tyrosine phosphatase SHP2. We also have microinjected reagents which target proteins involved in the formation of rasGTP and which mediate some of the downstream e ects of ras activation. Reagents which target the formation of rasGTP (Shc and dominant negative ras protein) inhibit DNA synthesis only at points early in G 1 , as do reagents which target components of the MAP kinase pathway. Injection of antibodies to p21ras itself, or a recombinant Raf-1 protein domain which binds to the e ector region of ras in a GTP-dependent manner, results in the inhibition of cell cycle progression throughout G 1 phase. The results point to a continuous requirement for both PI 3-k and ras activity until cellular commitment to DNA synthesis, although some of the molecules which are both upstream and downstream of these activities are only required transiently. Our results are also consistent with a Raf-1 independent ras activity late in G 1 , as well as IRS-1 independent e ects of PI 3-kinase.

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Potent Stimulation of SH-PTP2 Phosphatase Activity by Simultaneous Occupancy of Both SH2 Domains

Cited by 269 publications

References 25 publications

SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis

SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

Prolonged vs transient roles for early cell cycle signaling components

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