Cellular Redistribution of Protein Tyrosine Phosphatases LAR and PTPσ by Inducible Proteolytic Processing

Aicher, Babette; Lerch, Markus M.; Müller, Thomas; Schilling, James; Ullrich, Axel

doi:10.1083/jcb.138.3.681

Cited by 147 publications

(134 citation statements)

References 64 publications

(91 reference statements)

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…RPTPe, related to RPTPa, exists in both cytoplasmic and trans-membrane forms (Elson and Leder, 1995a). Furthermore, cleavage of the ectodomain of membrane PTPs can induce cellular redistribution of the catalytic domain (Aicher et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

et al. 2000

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

et al. 2000

View full text Add to dashboard Cite

“…Second, PTPRS is specifically microdeleted in 26% of head and neck cancer patients (34). Third, PTPRS function is modulated by shedding (35) suggesting that its tumor suppressor activity could be abrogated by ADAM17-mediated shedding. Finally, MEDI3622-mediated inhibition of ADAM17 rescues PTPRS in the OE21 model.…”

Section: Discussionmentioning

confidence: 99%

A Monoclonal Antibody to ADAM17 Inhibits Tumor Growth by Inhibiting EGFR and Non–EGFR-Mediated Pathways

Rios-Doria¹,

Sabol²,

Chesebrough³

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

ADAM17 is the primary sheddase for HER pathway ligands. We report the discovery of a potent and specific ADAM17 inhibitory antibody, MEDI3622, which induces tumor regression or stasis in many EGFR-dependent tumor models. The inhibitory activity of MEDI3622 correlated with EGFR activity both in a series of tumor models across several indications as well in as a focused set of head and neck patient-derived xenograft models. The antitumor activity of MEDI3622 was superior to that of EGFR/HER pathway inhibitors in the OE21 esophageal model and the COLO205 colorectal model suggesting additional activity outside of the EGFR pathway. Combination of MEDI3622 and cetuximab in the OE21 model was additive and eradicated tumors. Proteomics analysis revealed novel ADAM17 substrates that function outside of the HER pathways and may contribute toward the antitumor activity of the monoclonal antibody.

show abstract

“…Because protein tyrosine phosphatases and EGFR colocalize to E-cadherin-containing cellcell contacts in human epidermoid carcinoma cells (1,57) and in breast cancer cells (58), we examined whether E-cadherin decreases EGFR phosphorylation via a pathway involving a protein tyrosine phosphatase. A protein tyrosine phosphatase inhibitor, sodium orthovanadate, increased EGFR tyrosine phosphorylation markedly in dense cultures treated with TGF-␣ without affecting total levels of EGFR (Fig.…”

Section: E-cadherin-dependent Mucin Production Is Associated With Decmentioning

confidence: 99%

“…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. …”

mentioning

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

View full text Add to dashboard Cite

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...

show abstract

Cellular Redistribution of Protein Tyrosine Phosphatases LAR and PTPσ by Inducible Proteolytic Processing

Cited by 147 publications

References 64 publications

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

A Monoclonal Antibody to ADAM17 Inhibits Tumor Growth by Inhibiting EGFR and Non–EGFR-Mediated Pathways

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

Contact Info

Product

Resources

About