Protein tyrosine phosphatase 1B interacts with the activated insulin receptor

Seely, B. L.; Staubs, P. A.; Reichart, D. R.; Berhanu, P.; Milarski, K. L.; Saltiel, A. R.; Kusari, Jyotirmoy; Olefsky, J. M.

doi:10.2337/diabetes.45.10.1379

Cited by 141 publications

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“…The largest single pool is localized to the cytoplasmic face of the endoplasmic reticulum through a carboxyl-terminal domain (20). PTP1B also interacts with the insulin receptor and the EGF receptor and is phosphorylated on tyrosine residues in response to receptor stimulation (21)(22)(23). We have also reported that PTP1B is physically and functionally associated with focal adhesion complexes (24).…”

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confidence: 82%

Essential Tyrosine Residues for Interaction of the Non-receptor Protein-tyrosine Phosphatase PTP1B with N-cadherin

Rhee

Lilien

Balsamo

2001

Journal of Biological Chemistry

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Expression of a dominant-negative, catalytically inactive form of the nonreceptor protein-tyrosine phosphatase PTP1B in L-cells constitutively expressing N-cadherin results in loss of N-cadherin-mediated cell-cell adhesion. PTP1B interacts directly with the cytoplasmic domain of N-cadherin, and this association is regulated by phosphorylation of tyrosine residues in PTP1B. The following three tyrosine residues in PTP1B are potential substrates for tyrosine kinases: Tyr-66, Tyr-152, and Tyr-153. To determine the tyrosine residue(s) that are crucial for the cadherin-PTP1B interaction we used sitedirected mutagenesis to create catalytically inactive PTP1B constructs bearing additional single, double, or triple mutations in which tyrosine was substituted by phenylalanine. Mutation Y152F eliminates binding to N-cadherin in vitro, whereas mutations Y66F and Y153F do not. Overexpression of the catalytically inactive PTP1B with the Y152F mutation in L-cells constitutively expressing N-cadherin has no effect on N-cadherin-mediated adhesion, and immunoprecipitation reveals that the mutant Y152F PTP1B does not associate with Ncadherin in situ. Furthermore, among cells overexpressing the Y152F mutant endogenous PTP1B associates with N-cadherin and is tyrosine-phosphorylated.Members of the cadherin family of cell-cell adhesion molecules are key players in morphogenetic processes, and regulation of cadherin function, as opposed to transcription and translation, is thought to be responsible for many of the rapid changes that occur during development. Classic cadherins are characterized by a highly conserved intracellular domain that interacts with the actin-containing cytoskeleton, an interaction essential for function. This interaction is mediated by ␣-and ␤-catenin (1-4); ␤-catenin associates directly with a 20-amino acid domain near the carboxyl terminus of cadherin (5, 6) and with ␣-catenin, which, in turn, interacts with actin, either directly (7) or indirectly, through ␣-actinin (8). ␤-catenin not only performs a bridging role between cadherin and actin, but free ␤-catenin can be translocated to the nucleus where it regulates transcription of cadherin and other gene products (9, 10). Thus, the regulation of free ␤-catenin is of critical importance, and, consequently, the interaction of ␤-catenin with cadherin has multiple ramifications on cellular function (11,12).Regulation of the interaction of ␤-catenin with N-cadherin is mediated by the phosphorylation of tyrosine residues on ␤-catenin (13, 14). In embryonic chick neural retina cells, hyperphosphorylation of ␤-catenin is correlated with loss of its association with N-cadherin and loss of cadherin function (13,14). Enhanced phosphorylation of ␤-catenin has also been correlated with loss of E-cadherin function (15)(16)(17)(18)(19). These data suggest that tyrosine kinases and/or phosphatases must play a critical role in maintaining ␤-catenin association with cadherin and/or its ability to mediate the cytoskeletal linkage. We have reported that the nonreceptor protein-t...

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confidence: 82%

Essential Tyrosine Residues for Interaction of the Non-receptor Protein-tyrosine Phosphatase PTP1B with N-cadherin

Rhee

Lilien

Balsamo

2001

Journal of Biological Chemistry

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“…Microinjection of PTP-1B into Xenopus oocytes blocked insulin-stimulated S6 peptide phosphorylation and retarded insulin-induced oocyte maturation (45). Subsequent studies demonstrated that overexpression of PTP-1B affected insulin-or insulin-like growth factor-I-dependent tyrosine phosphorylation and metabolic responses such as glucose incorporation into glycogen (37) and that PTP-1B and IR interacted physically (46). Recently, PTP-1B-deficient (knockout) mice were shown to have an increased phosphorylation of IR and IRS-1 in liver and muscle tissue after insulin injection as well as a resistance to weight gain in mice, suggesting that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism (16).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Protein-tyrosine Phosphatases in Rat Adipocytes

Calera

Vallega

Pilch

2000

Journal of Biological Chemistry

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Protein-tyrosine phosphatases (PTPases) play a key role in maintaining the steady-state tyrosine phosphorylation of the insulin receptor (IR) and its substrate proteins such as insulin receptor substrate 1 (IRS-1). However, the PTPase(s) that inactivate IR and IRS-1 under physiological conditions remain unidentified. Here, we analyze the subcellular distribution in rat adipocytes of several PTPases thought to be involved in the counterregulation of insulin signaling. We found that the transmembrane enzymes, protein-tyrosine phosphatase (PTP)-␣ and leukocyte common antigen-related (LAR), were detected predominantly in the plasma membrane and to a lesser extent in the heavy microsomes, a distribution similar to that of insulin receptor. PTP-1B and IRS-1 were present in light microsomes and cytosol, whereas SHPTP2/Syp was exclusively cytosolic. Insulin induced a redistribution of PTP-␣ from the plasma membrane to the heavy microsomes in a parallel fashion with the receptor. The distribution of PTP-1B in the light microsomes from resting adipocytes was similar to that of IRS-1 as determined by sucrose velocity gradient fractionation. Analysis of the catalytic activity of partially purified rat adipocyte PTP-␣ and LAR and recombinant PTP-1B showed that all three PTPases dephosphorylate IR. When a mix of IR/IRS-1 was used as a substrate, PTP-1B was particularly effective in dephosphorylating IRS-1. Considering that IR and IRS-1 can be dephosphorylated in internal membrane compartments from rat adipocytes (Kublaoui, B., Lee, J., and Pilch, P.F. (1995) J. Biol. Chem. 270, 59 -65) and that PTP-␣ and PTP-1B are the respective PTPases in these fractions, we conclude that these PTPases are responsible for the counterregulation of insulin signaling there, whereas both LAR and PTP-␣ may act upon cell surface insulin receptors.The initial steps in insulin signaling require protein tyrosine phosphorylation. The interaction of insulin with its plasma membrane receptor elicits a rapid autophosphorylation on specific tyrosine residues in several domains of the receptor's cytoplasmic ␤-subunit followed by activation of the receptor's exogenous tyrosine kinase activity as reflected by enhanced substrate phosphorylation (reviewed in Refs. 1 and 2). The principle insulin receptor substrates (IRSs) 1 involved in metabolic regulation are IRS-1 and IRS-2, and there is abundant biochemical evidence to support this (reviewed in Ref.3). Genetic evidence from animals devoid of IRS-1 (4, 5) and IRS-2 (6) further suggests that these molecules are intimately involved in the signaling to metabolic pathways regulated by insulin. Two additional members of the IRS family, IRS-3 and IRS-4, have been described, but they are unlikely to be involved in insulin-dependent metabolic regulation because the former is not expressed in the appropriate tissues (7) and a knockout of the latter has no obvious metabolic phenotype (8). IRS-1 and IRS-2 contain numerous tyrosine residues that, when phosphorylated, act as docking sites for a certain set of Src homolo...

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“…Even though there is an abundance of experimental evidence indicating that PTP1B acts as a negative regulator of insulin signaling, direct interaction of PTP1B with the IR, which is crucial for dephosphorylation of the activated IR, has been documented only in cultured cell systems or in vitro studies (5,12,21,35,36,43). For example, with use of brown adipocyte culture, the direct interaction between wild-type PTP1B and the IR was demonstrated in insulin-stimulated cells (35).…”

Section: Ajp-endocrinol Metabmentioning

confidence: 99%

“…Mechanistic studies of PTP1B's action suggest that interaction between PTP1B and the IR is important for catalyzing IR dephosphorylation (5,11,12,23,36,43). Receptor tyrosine kinases appear to undergo internalization and form complexes with PTP1B, thereby removing phosphate groups from tyrosine residues (23).…”

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confidence: 99%

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

Suryawan

Davis

2003

American Journal of Physiology-Endocrinology and Metabolism

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Suryawan, Agus, and Teresa A. Davis. Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs. Am J Physiol Endocrinol Metab 284: E47-E54, 2003. First published September 11, 2002 10.1152/ajpendo.00210.2002The high activity of the insulin-signaling pathway contributes to the enhanced feeding-induced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein-tyrosine-phosphatase 1B (PTP1B) is a negative regulator of the tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1). The activity of PTP1B is determined mainly by its association with IR and Grb2. We examined the level of PTP1B activity, PTP1B protein abundance, PTP1B tyrosine phosphorylation, and the association of PTP1B with IR and Grb2 in skeletal muscle and liver of fasted and fed 7-and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P Ͻ 0.05) in 7-compared with 26-day-old pigs but in liver was similar in the two age groups. PTP1B abundances were similar in muscle but lower (P Ͻ 0.05) in liver of 7-compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P Ͻ 0.05) in 7-than in 26-day-old pigs. The associations of PTP1B with IR and with Grb2 were lower (P Ͻ 0.05) at 7 than at 26 days of age in muscle, but there were no age effects in liver. Finally, in both age groups, fasting did not have any effect on these parameters. These results indicate that basal PTP1B activation is developmentally regulated in skeletal muscle of neonatal pigs, consistent with the developmental changes in the activation of the insulin-signaling pathway reported previously. Reduced PTP1B activation in neonatal muscle likely contributes to the enhanced insulin sensitivity of skeletal muscle in neonatal pigs.neonate; insulin signaling; insulin sensitivity; protein synthesis THE ENHANCED ACTIVATION of the insulin-signaling pathway leading to translation initiation in skeletal muscle of the neonate after food consumption has an important role in the enhanced responsiveness of muscle protein synthesis to feeding in the neonate (13,16,26,27,37). We have shown that the feeding-induced activation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3-kinase (PI 3-kinase), as well as the abundance of the IR, is enhanced in skeletal muscle of the neonatal pig and decreases markedly with development. This developmental decline in the feeding-induced activation of early insulin-signaling components parallels the developmental decline in the feeding-induced activation of downstream signaling proteins, leading to the stimulation of protein synthesis in skeletal muscle and the developmental decrease in the ability of insulin to stimulate muscle protein synthesis. However, the molecular mechanism that regulates the developmental decline in the insulin sensitivity of skeletal muscle in neonatal pigs has not been elucidated.When insulin binds to its receptor, it induces autophosphorylation of the receptor on its ty...

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Protein tyrosine phosphatase 1B interacts with the activated insulin receptor

Cited by 141 publications

References 0 publications

Essential Tyrosine Residues for Interaction of the Non-receptor Protein-tyrosine Phosphatase PTP1B with N-cadherin

Essential Tyrosine Residues for Interaction of the Non-receptor Protein-tyrosine Phosphatase PTP1B with N-cadherin

Dynamics of Protein-tyrosine Phosphatases in Rat Adipocytes

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

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