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

Rhee, Jae-Ho; Lilien, Jack; Balsamo, Janne

doi:10.1074/jbc.m007656200

Cited by 42 publications

(47 citation statements)

References 31 publications

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“…PTP1B associates directly with the cytoplasmic domain of N-cadherin, as does the dominant-negative construct (Balsamo et al, 1996Rhee et al, 2001, Xu et al, 2002. We have recently determined the binding site on the cytoplasmic domain to which PTP1B is targeted (Xu et al, 2002).…”

Section: Maintaining Stable Adhesions: the Nonreceptor Tyrosine Kinasmentioning

confidence: 99%

“…Targeting is thus crucial for its proper functioning within cells. Interaction with Ncadherin depends on phosphorylation of tyrosine 152 in PTP1B (Rhee et al, 2001); alanine substitution of this residue abolishes the dominant-negative effect of the C215S mutant PTP1B and prevents localization at cell boundaries. Thus, an additional feature of this set of regulatory interactions is the potential to regulate the phosphorylation of PTP1B and, therefore, its association with cadherin and the content of phosphorylated tyrosine residues on ␤-catenin.…”

Section: Maintaining Stable Adhesions: the Nonreceptor Tyrosine Kinasmentioning

confidence: 99%

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Turn‐off, drop‐out: Functional state switching of cadherins

Lilien

Balsamo

Arregui

et al. 2002

Developmental Dynamics

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149

116

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The classic cadherins are a group of calcium dependent, homophilic cell-cell adhesion molecules that drive morphogenetic rearrangements and maintain the integrity of cell groups through the formation of adherens junctions. The formation and maintenance of cadherin-mediated adhesions is a multistep process and mechanisms have evolved to regulate each step. This suggests that functional state switching plays an important role in development. Among the many challenges ahead is to determine the developmental role that functional state switching plays in tissue morphogenesis and to define the roles of each of the several regulatory interactions that participate in switching. One correlate of the loss of cadherinmediated adhesion, the "turn-off" of cadherin function, is the exit, or "drop-out" of cells from neural and epithelial layers and their conversion to a motile phenotype. We suggest that epithelial mesenchymal conversions may be initiated by signaling pathways that result in the loss of cadherin function. Tyrosine phosphorylation of ␤-catenin is one such mechanism. Enhanced phosphorylation of tyrosine residues on ␤-catenin is almost invariably associated with loss of the cadherin-actin connection concomitant with loss of adhesive function. There are several tyrosine kinases and phosphatases that have been shown to have the potential to alter the phosphorylation state of ␤-catenin and thus the function of cadherins. Our laboratory has focused on the role of the nonreceptor tyrosine phosphatase PTP1B in regulating the phosphorylation of ␤-catenin on tyrosine residues. Our data suggest that PTP1B is crucial for maintenance of N-cadherin-mediated adhesions in embryonic neural retina cells. By using an L-cell model system constitutively expressing N-cadherin, we have worked out many of the molecular interactions essential for this regulatory interaction. Extracellular cues that bias this critical regulatory interaction toward increased phosphorylation of ␤-catenin may be a critical component of many developmental events.

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Section: Maintaining Stable Adhesions: the Nonreceptor Tyrosine Kinasmentioning

confidence: 99%

Section: Maintaining Stable Adhesions: the Nonreceptor Tyrosine Kinasmentioning

confidence: 99%

Turn‐off, drop‐out: Functional state switching of cadherins

Lilien

Balsamo

Arregui

et al. 2002

Developmental Dynamics

Self Cite

149

116

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“…Similarly, in human breast carcinoma cells, E-cadherin inhibits EGFR activation via protein tyrosine phosphatase activation (55). EGFR and several protein tyrosine phosphatases reported to dephosphorylate EGFR (27,34,46,57) colocalize to E-cadherin-containing adherens junctions (1,47,58,65), suggesting that E-cadherin may modulate EGFR phosphotyrosine levels via recruitment of an EGFR-directed protein tyrosine phosphatase to adherens junctions. …”

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confidence: 99%

E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells

Kim¹,

Schein²,

Nadel³

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Kim, Suil, Aaron J. Schein, and Jay A. Nadel. E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 289: L1049 -L1060, 2005. First published July 29, 2005; doi:10.1152/ajplung.00388.2004In previous work, we showed that epidermal growth factor receptor (EGFR) activation causes mucin expression in airway epithelium in vivo and in human NCI-H292 airway epithelial cells and normal human bronchial epithelial (NHBE) cells in vitro. Here we show that the cell surface adhesion molecule, E-cadherin, promotes EGFR-mediated mucin production in NCI-H292 cells in a cell density-and cell cycle-dependent fashion. The addition of the EGFR ligand, transforming growth factor (TGF)-␣, increased MUC5AC protein expression markedly in dense, but not in sparse, cultures. MUC5AC-positive cells in dense cultures contained 2 N DNA content and did not incorporate bromodeoxyuridine, suggesting that they develop via cell differentiation and that a surface molecule involved in cell-cell contact is important for EGFRmediated mucin production. In support of this hypothesis, in dense cultures of NCI-H292 cells and in NHBE cells at air-liquid interface, blockade of E-cadherin-mediated cell-cell contacts decreased EGFRdependent mucin production. E-cadherin blockade also increased EGFR-dependent cell proliferation and TGF-␣-induced EGFR tyrosine phosphorylation in dense cultures of NCI-H292 cells, suggesting that E-cadherin promotes EGFR-dependent mucin production and inhibits EGFR-dependent cell proliferation via modulation of EGFR phosphotyrosine levels. Furthermore, in dense cultures, E-cadherin blockade decreased the rate of EGFR tyrosine dephosphorylation, implicating an E-cadherin-dependent protein tyrosine phosphatase in EGFR dephosphorylation. Thus E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC production, and our results suggest that this occurs via a pathway involving protein tyrosine phosphatase-dependent EGFR dephosphorylation. epidermal growth factor receptor; airway epithelium THE PRODUCTION OF MUCIN-CONTAINING goblet cells in the airways is an important feature in diseases of mucus hypersecretion such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, nasal polyps, and bronchiectasis (reviewed in Ref. 38). Several years ago, Takeyama et al. (61) showed that epidermal growth factor receptor (EGFR) activation causes mucin production in airway epithelial cells in vivo and in human NCI-H292 airway epithelial cells in vitro. Subsequent studies have implicated EGFR activation in mucin upregulation (44) by many stimuli (7, 24, 26, 31, 32, 50 -52, 60, 62), suggesting that the EGFR cascade is a convergent pathway for mucin production by airway epithelial (goblet) cells.Biological responses to EGFR signaling are pleiotropic and include proliferation, differentiation, and apoptosis (reviewed in Ref. 19). In multicellular organisms, cell neighbors influence cell growth and differentiation. When normal e...

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“…A role for PTP1B in the regulation of many cellular functions has been suggested, including integrin (20 -23), cadherin (24,25), and cytokine receptor signaling (26 -28), cell cycle regulation (29 -31), and the response to cellular stress (32). Multiple studies indicated that PTP1B dephosphorylates the EGFR (16,17) and the insulin receptor (IR) (14,(33)(34)(35).…”

mentioning

confidence: 99%

Regulation of Receptor Tyrosine Kinase Signaling by Protein Tyrosine Phosphatase-1B

Haj

Markova

Klaman

et al. 2003

Journal of Biological Chemistry

237

204

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Receptor tyrosine kinases (RTKs) are key regulators of cellular homeostasis. Based on in vitro and ex vivo studies, protein tyrosine phosphatase-1B (PTP1B) was implicated in the regulation of several RTKs, yet mice lacking PTP1B show defects mainly in insulin and leptin receptor signaling. To address this apparent paradox, we studied RTK signaling in primary and immortalized fibroblasts from PTP1B ؊/؊ mice. After growth factor treatment, cells lacking PTP1B exhibit increased and sustained phosphorylation of the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR). However, Erk activation is enhanced only slightly, and there is no increase in Akt activation in PTP1B-deficient cells. Our results show that PTP1B does play a role in regulating EGFR and PDGFR phosphorylation but that other signaling mechanisms can largely compensate for PTP1B deficiency. In-gel phosphatase experiments suggest that other PTPs may help to regulate the EGFR and PDGFR in PTP1Bfibroblasts. This and other compensatory mechanisms prevent widespread, uncontrolled activation of RTKs in the absence of PTP1B and probably explain the relatively mild effects of PTP1B deletion in mice.Regulation of cellular proliferation, adhesion, and migration is pivotal for maintaining homeostasis. Multiple peptide growth factors direct these processes to differing extents in primary fibroblasts and fibroblast cell lines. These growth factors signal via receptors with intrinsic protein-tyrosine kinase activity, termed receptor tyrosine kinases (RTKs).1 Ligand binding activates the intrinsic kinase activity of these receptors, resulting in the phosphorylation of multiple receptor tyrosyl residues. These serve as docking sites to recruit signal relay molecules containing src homology-2 and/or phosphotyrosine binding domains, most of which also are RTK substrates. Based largely on experiments in which wild-type PTPs or their catalytically impaired (dominant-negative) mutants were overexpressed, multiple PTPs, including LAR (7), DEP-1 (8), TC-PTP (9, 10), Shp-1 (11, 12), Shp-2 (13), and PTP1B (14 -17) have been implicated in the dephosphorylation of various RTKs. Which, if any, of these PTPs regulate RTK signaling under physiologically relevant conditions of expression has remained largely unclear. Also unknown is the extent to which RTK dephosphorylation, as opposed to other down-regulatory mechanisms such as RTK degradation and/or inhibitory seryl phosphorylation, plays the (a) key role in receptor inactivation.PTP1B is a widely expressed non-receptor PTP that is localized on intracellular membranes via a hydrophobic C-terminal targeting sequence (18,19). A role for PTP1B in the regulation of many cellular functions has been suggested, including integrin (20 -23), cadherin (24, 25), and cytokine receptor signaling (26 -28), cell cycle regulation (29 -31), and the response to cellular stress (32). Multiple studies indicated that PTP1B dephosphorylates the EGFR (16, 17) and the insulin receptor (IR) (14,(33)(34)(35). Analy...

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

Cited by 42 publications

References 31 publications

Turn‐off, drop‐out: Functional state switching of cadherins

Turn‐off, drop‐out: Functional state switching of cadherins

E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells

Regulation of Receptor Tyrosine Kinase Signaling by Protein Tyrosine Phosphatase-1B

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