Characterization of a 115-kDa Protein That Binds to SH-PTP2, a Protein-tyrosine Phosphatase with Src Homology 2 Domains, in Chinese Hamster Ovary Cells

Noguchi, Tetsuya; Matozaki, Takashi; Fujioka, Yohsuke; Yamao, Takuji; Tsuda, Masahiro; Takada, Toshiyuki; Kasuga, Masato

doi:10.1074/jbc.271.44.27652

Cited by 61 publications

(66 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, LPA induced a rapid increase in both the extent of tyrosine phosphorylation of SHPS-1 and the amount of SHP-2 associated with SHPS-1; these e ects peaked at *5 min and thereafter declined (Figure 1a). SHPS-1 has been suggested to be a substrate for the phosphatase activity of SHP-2 Noguchi et al, 1996;Kharitonenkov et al, 1997); thus, after binding to phosphorylated SHPS-1 in response to LPA, SHP-2 may catalyze SHPS-1 dephosphorylation. The e ect of LPA on both tyrosine phosphorylation of SHPS-1 and its association with SHP-2 increased in a concentration-dependent manner, being maximal at 1 mM LPA (Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

“…We have recently characterized a membrane glycoprotein, SHPS-1 (SHP substrate-1) Noguchi et al, 1996;Yamao et al, 1997) (also known as SIRP1 (Kharitonenkov et al, 1997) or BIT (Ohnishi et al, 1996)), whose extracellular region contains three homologous immunoglobulin-like domains and multiple N-linked glycosylation sites. The cytoplasmic region of SHPS-1 contains four tyrosine residues followed by XX(L/V/I) sequences (Y408ADL, Y432ASI, Y449ADL and Y473ASV), which represent potential tyrosine phosphorylation sites.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the SH2 domains of SHP-2 may bind to one or more phosphorylated tyrosine residues in the cytoplasmic domain of SHPS-1. The extent of tyrosine phosphorylation of SHPS-1 is greatly increased in cells that overexpress catalytically inactive SHP-2 (Cys 459 to Ser) Noguchi et al, 1996). Thus, SHPS-1 may be a target for the phosphatase activity of SHP-2, although this form of a catalytically inactive SHP-2 is not a substrate trapping mutant (Flint et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 1998

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 1998

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hence, our model of SHP-2/IRS-1 interactions is consistent with the emerging model of SHP-2/gp130 interaction; mutation of the SHP-2 binding sites in gp130 (the shared subunit of many IL-6-type cytokine receptors) prolongs activation of the associated JAK tyrosine kinase and the downstream STAT signaling proteins during oligomerization of gp130 or during CNTF signaling (39 -41). SHP-2 also binds and dephosphorylates other classes of tyrosyl phosphoproteins, including the SIRP/SHPS proteins and an approximately 95-100-kDa GAB-1-like tyrosyl-phosphorylated docking protein (p95-100) (42)(43)(44)(45)(46)(47)(48)(49)(50)(51). Although, like IRS-1, these SHP-2 binding proteins are dephosphorylated by SHP-2, dephosphorylation in this case correlates with increased MAP kinase activation and proliferation.…”

Section: Fig 2 Insulin-stimulated Tyrosine Phosphorylation and Shp-mentioning

confidence: 99%

The COOH-terminal Tyrosine Phosphorylation Sites on IRS-1 Bind SHP-2 and Negatively Regulate Insulin Signaling

Myers¹,

Méndez²,

Shi³

et al. 1998

Journal of Biological Chemistry

152

View full text Add to dashboard Cite

Activation of tyrosine kinases by numerous growth factor and cytokine receptors leads to tyrosine phosphorylation of the insulin receptor substrate (IRS)-proteins. Tyrosine-phosphorylated motifs on the IRS proteins bind to the SH2 domains in proteins that mediate downstream signals, including phosphatidylinositol 3-kinase, GRB-2, and SHP-2. We investigated the function of the two SHP-2 binding COOH-terminal tyrosines of IRS-1 by replacing them with phenylalanine (IRS-1 FCT ). IRS-1FCT failed to bind SHP-2 or mediate its tyrosine phosphorylation during insulin stimulation. Although several reports suggest a critical role for SHP-2 in insulin stimulated mitogen-activated protein kinase activation and cell proliferation, IRS-1 FCT mediated these effects normally in 32D cells. Indeed, IRS-1 FCT exhibited increased tyrosine phosphorylation, phosphatidylinositol 3-kinase binding and activation of protein synthesis in response to insulin. These results suggest that SHP-2 attentuates the phosphorylation and downstream signal transmission of IRS-1 and that the interaction of IRS-1 and SHP-2 is an important regulatory event which attenuates insulin metabolic responses.Insulin transmits cellular signals by binding the cell surface insulin receptor and activating the insulin receptor tyrosine kinase (1). The activated tyrosine kinase transmits downstream signals largely through the action of a class of intermediary docking proteins, including GAB-1, Shc, and a set of signaling molecules known as the insulin receptor substrate (IRS) 1 proteins, IRS-1, IRS-2, IRS-3, and IRS-4 (2-6). The NH 2 -terminal region of the IRS proteins contains extended domains that cooperate in receptor recognition (1, 2, 7), while the COOH-terminal region possesses numerous tyrosine-containing motifs that become phosphorylated and bind specific Src homology 2 (SH2) domains in signaling proteins during insulin stimulation. While each IRS protein contains unique tyrosine phosphorylation sites, three classes of sites are well conserved across the IRS proteins, multiple YMXM motifs responsible for binding regulatory subunits of phosphatidylinsositol (PI) 3Ј-kinase, a YXNX motif that binds GRB-2, and a pair of COOH-terminal motifs (YIDL and YASI) responsible for binding the SHP-2 tyrosine phosphatase. The role of the PI 3Ј-kinase and GRB-2 binding motifs on IRS-1 have been extensively studied, but the role of the SHP-2 binding sites in IRS-1 signaling is unclear (1).SHP-2 is a cytoplasmic protein tyrosine phosphatase that contains two SH2 domains (8). It is ubiquitously expressed in mammalian cells and appears to be the homolog of the Drosophila corkscrew gene responsible for activation of p21 ras downstream of a variety of tyrosine kinases (9, 10). Coordinate binding of the two SH2 domains of SHP-2 to double tyrosine motifs in target proteins such as IRS-1 increases the affinity of the association and activates the phosphatase by moving the NH 2 -terminal SH2 domain away from the phosphatase active site (11)(12)(13)(14).Homozygous disruption of SHP-2 i...

show abstract

“…For instance, in Chinese hamster ovary cells expressing insulin receptors, SHP-2 attenuates insulin metabolic responses by reducing insulin receptor substrate-1 tyrosine phosphorylation. 27 SH-PTP2 also acts as a negative regulator in both platelet-derived growth factor (PDGF) receptor-mediated signalling and the RAS pathway in T-cell receptor cascade. 28,29 In addition, SH-PTP2 has been shown to negatively regulate EGFR signalling in cells which overexpress EGFR, such as tumour cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells

et al. 2005

View full text Add to dashboard Cite

Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.

show abstract

Characterization of a 115-kDa Protein That Binds to SH-PTP2, a Protein-tyrosine Phosphatase with Src Homology 2 Domains, in Chinese Hamster Ovary Cells

Cited by 61 publications

References 33 publications

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

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

The COOH-terminal Tyrosine Phosphorylation Sites on IRS-1 Bind SHP-2 and Negatively Regulate Insulin Signaling

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells

Contact Info

Product

Resources

About