Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor (EGF) receptor through a Src homology 3 (SH3) domain-mediated association with Grb2

Charest, Alain; Wagner, John; Kwan, Mei; Tremblay, Michel L.

doi:10.1038/sj.onc.1201008

Cited by 49 publications

(37 citation statements)

References 31 publications

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“…For example, GRB2 binds by a multisite interaction with tyrosine-phosphorylated LRP (RPTP-␣), and this interaction can also mediate the activation by GRB2 of signaling through the Sos pathway (30,31). In addition, GRB2 associates with SH2 domain-containing PTPases in a variety of cell types (32)(33)(34) as well as with PTP-PEST (35). These data suggest that GRB2 may have an important cellular role in the regulation of PTPase activities as well as their association with other signaling proteins with potentially important effects on substrate localization or complex formation that influences the rate of dephosphorylation of various PTPase substrates.…”

Section: Fig 4 Binding Of Sh2 Domain-containing Adaptor Proteins Tomentioning

confidence: 92%

Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B

Goldstein

Bittner-Kowalczyk

White

et al. 2000

Journal of Biological Chemistry

379

221

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Regulation of the steady-state tyrosine phosphorylation of the insulin receptor and its postreceptor substrates are essential determinants of insulin signal transduction. However, little is known regarding the molecular interactions that influence the balance of these processes, especially the phosphorylation state of postinsulin receptor substrates, such as insulin receptor substrate-1 (IRS-1). The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1B (PTP1B), SH2 domain-containing PTPase-2 (SHP-2), leukocyte common antigen-related (LAR), and leukocyte antigen-related phosphatase) (LRP) toward IRS-1 dephosphorylation was studied using recombinant proteins in vitro. PTP1B exhibited the highest specific activity (percentage dephosphorylated per g per min), and the enzyme activities varied over a range of 5.5 ؋ 10 3 . When evaluated as a ratio of activity versus IRS-1 to that versus p-nitrophenyl phosphate, PTP1B remained significantly more active by 3.1-293-fold, respectively. Overlay blots with recombinant Src homology 2 domains of IRS-1 adaptor proteins showed that the loss of IRS-1 binding of Crk, GRB2, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase paralleled the rate of overall IRS-1 dephosphorylation. Further studies revealed that the adaptor protein GRB2 strongly promoted the formation of a stable protein complex between tyrosine-phosphorylated IRS-1 and catalytically inactive PTP1B, increasing their co-immunoprecipitation from an equimolar solution by 13.5 ؎ 3.3-fold (n ‫؍‬ 7; p < 0.01). Inclusion of GRB2 in a reaction mixture of IRS-1 and active PTP1B also increased the overall rate of IRS-1 tyrosine dephosphorylation by 2.7-3.9-fold (p < 0.01). These results provide new insight into novel molecular interactions involving PTP1B and GRB2 that may influence the steady-state capacity of IRS-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling. Cellular protein-tyrosine phosphatases (PTPases)1 play a crucial role in maintaining the steady-state phosphotyrosine content of proteins in the insulin action pathway (1, 2). Much of the available evidence characterizing the role of PTPases in insulin signaling has focused on the regulation of the activation state of the insulin receptor itself, where several PTPases, in particular the intracellular enzyme PTP1B and the transmembrane homologs LAR and LRP (RPTP-␣), have been postulated to have a regulatory function (3-6). However, the identity of PTPase(s) that regulate the tyrosine phosphorylation state of substrates of the insulin receptor kinase, such as IRS-1, has not been determined. IRS-1 is phosphorylated on multiple tyrosine residues by the activated insulin receptor kinase and serves as a docking site or scaffold for a series of adaptor proteins that possess Src homology 2 (SH2) domains (7). These proteins bind to specific phosphotyrosine sites on IRS-1, become activated, and transmit the downstream signal from the insulin receptor to various met...

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Section: Fig 4 Binding Of Sh2 Domain-containing Adaptor Proteins Tomentioning

confidence: 92%

Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B

Goldstein

Bittner-Kowalczyk

White

et al. 2000

Journal of Biological Chemistry

379

221

View full text Add to dashboard Cite

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“…Candidate phosphatases include PTP1B and PTP-PEST, which have been shown to directly interact with and dephosphorylate Cas (50,51). Interestingly, PTP-PEST was recently demonstrated to become recruited to activated EGF receptor complexes (52). In one study, insulininduced tyrosine dephosphorylation of FAK and paxillin was found to be mediated by protein phosphatase SHP2 (Ref.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Modulates Tyrosine Phosphorylation of p130Cas

Ojaniemi¹,

Vuori

1997

Journal of Biological Chemistry

103

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“…This hypothesis is currently being tested. 2 Tyrosine 344 of PSTPIP is found in a YASI motif. We tested several SH2 domains for their ability to bind phosphorylated PSTPIP and we found that the SH2 domains of c-Abl, and of the Src kinases c-Src and Fyn are capable of such a function in vitro.…”

Section: Fig 5 Binding Of the Cth Domain Of Ptp-pest To Pstpip Is Ementioning

confidence: 99%

“…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%

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.

show abstract

Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor (EGF) receptor through a Src homology 3 (SH3) domain-mediated association with Grb2

Cited by 49 publications

References 31 publications

Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B

Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B

Epidermal Growth Factor Modulates Tyrosine Phosphorylation of 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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