Furin-, ADAM 10-, and γ-Secretase-Mediated Cleavage of a Receptor Tyrosine Phosphatase and Regulation of β-Catenin's Transcriptional Activity

Anders, Lars; Mertins, Philipp; Lammich, Sven; Murgia, Marta; Hartmann, Dieter; Säftig, Paul; Haass, Christian; Ullrich, Axel

doi:10.1128/mcb.26.10.3917-3934.2006

Cited by 97 publications

(116 citation statements)

References 51 publications

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“…This event is followed by γ-secretase-dependent cleavage of the remaining transmembrane part of RPTP-κ to release the catalytic phosphatase intracellular (PIC) fragment from the membrane, thereby allowing its nuclear translocation. PIC of RPTP-κ is an active PTP that binds to and dephosphorylates its substrate β-catenin in the nucleus, which enhances transcriptional activity of β-catenin (Anders et al 2006).…”

Section: Rptp-κ and The R2b Subfamilymentioning

confidence: 99%

Receptor type protein tyrosine phosphatases (RPTPs) – roles in signal transduction and human disease

Fisher

2012

J. Cell Commun. Signal.

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Protein tyrosine phosphorylation is a fundamental regulatory mechanism controlling cell proliferation, differentiation, communication, and adhesion. Disruption of this key regulatory mechanism contributes to a variety of human diseases including cancer, diabetes, and auto-immune diseases. Net protein tyrosine phosphorylation is determined by the dynamic balance of the activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Mammals express many distinct PTKs and PTPs. Both of these families can be sub-divided into non-receptor and receptor subtypes. Receptor protein tyrosine kinases (RPTKs) comprise a large family of cell surface proteins that initiate intracellular tyrosine phosphorylationdependent signal transduction in response to binding of extracellular ligands, such as growth factors and cytokines. Receptor-type protein tyrosine phosphatases (RPTPs) are enzymatic and functional counterparts of RPTKs. RPTPs are a family of integral cell surface proteins that possess intracellular PTP activity, and extracellular domains that have sequence homology to cell adhesion molecules. In comparison to extensively studied RPTKs, much less is known about RPTPs, especially regarding their substrate specificities, regulatory mechanisms, biological functions, and their roles in human diseases. Based on the structure of their extracellular domains, the RPTP family can be grouped into eight sub-families. This article will review one representative member from each RPTP sub-family.

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Section: Rptp-κ and The R2b Subfamilymentioning

confidence: 99%

Receptor type protein tyrosine phosphatases (RPTPs) – roles in signal transduction and human disease

Fisher

2012

J. Cell Commun. Signal.

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“…Inhibition of PTP activity by pervanadate treatment disrupts epithelial junctions and, interestingly, impairs E-cadherin-activated Src signaling . Although some studies have reported a role for cell-contact-associated PTPs in controlling the integrity and function of epithelial junctions (Anders et al, 2006;Espejo et al, 2010;Fuchs et al, 1996;Müller et al, 1999;Sheth et al, 2007), none of the identified PTPs has been shown to control junctional SFKs.…”

Section: Introductionmentioning

confidence: 99%

Receptor protein tyrosine phosphatase RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src signaling to cortactin

Truffi

Dubreuil

Liang

et al. 2014

Journal of Cell Science

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Epithelial junctions are fundamental determinants of tissue organization, subject to regulation by tyrosine phosphorylation. Homophilic binding of E-cadherin activates tyrosine kinases, such as Src, that control junctional integrity. Protein tyrosine phosphatases (PTPs) also contribute to cadherin-based adhesion and signaling, but little is known about their specific identity or functions at epithelial junctions. Here, we report that the receptor PTP RPTPa (human gene name PTPRA) is recruited to epithelial adherens junctions at the time of cell-cell contact, where it is in molecular proximity to E-cadherin. RPTPa is required for appropriate cadherin-dependent adhesion and for cyst architecture in three-dimensional culture. Loss of RPTPa impairs adherens junction integrity, as manifested by defective E-cadherin accumulation and peri-junctional F-actin density. These effects correlate with a role for RPTPa in cellular (c)-Src activation at sites of E-cadherin engagement. Mechanistically, RPTPa is required for appropriate tyrosine phosphorylation of cortactin, a major Src substrate and a cytoskeletal actin organizer. Expression of a phosphomimetic cortactin mutant in RPTPa-depleted cells partially rescues F-actin and E-cadherin accumulation at intercellular contacts. These findings indicate that RPTPa controls cadherinmediated signaling by linking homophilic E-cadherin engagement to cortactin tyrosine phosphorylation through c-Src.

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“…In addition, Maretzky et al reported that ADAM10 modulated the nuclear translocation of β-catenin through shedding of cadherin E, resulting in enhanced expression of cyclin D1 and c-Myc, thus leading to the promotion of proliferation (29). Furthermore, ADAM10 contribution to cell proliferation by increasing the transcriptional activity of β-catenin involves the action of receptor protein tyrosine phosphatases (30). In the present study, the expression and clinicopathological significance of ADAM10 in laryngeal Table III.…”

Section: Discussionmentioning

confidence: 77%

Clinical significance of ADAM10 expression in laryngeal carcinoma

You

Cao

et al. 2016

Oncology Letters

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Abstract. Recent findings suggest that upregulated a disintegrin and metalloproteinase (ADAM)10 expression participates in the progression of multiple types of cancer. However, the expression pattern and clinicopathological significance of ADAM10, and its potential prognostic role in laryngeal carcinoma remains to be explored. The present study firstly determined the significantly elevated expression status of ADAM10 protein and messenger RNA in laryngeal carcinoma tissues compared with that in adjacent non-tumor tissues by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. Next, the expression of ADAM10 and the proliferation marker Ki-67 was examined in 78 laryngeal carcinoma and 35 adjacent non-tumor specimens using immunohistochemistry. Overexpressed ADAM10 in laryngeal carcinoma was detected, which correlated with T classification (P<0.01), clinical stage (P<0.01), pathology (P=0.034) and Ki-67 expression (P<0.01). Furthermore, the expression of ADAM10 was positively correlated with the expression of Ki-67 (R 2 = 0.22; P<0.01). The Kaplan-Meier method revealed that the group with overexpressed ADAM10 exhibited shorter overall survival time compared with those with low ADAM10 expression. Our findings indicated that ADAM10 serves a notable role in the progression and prognosis of laryngeal carcinoma. IntroductionLaryngeal cancer is estimated to be the second most common malignancy of the head and neck, and it has a high mortality rate and a poor prognosis (1,2). The majority of laryngeal carcinoma patients are middle-aged males (3,4). The primary risk factors are endogenic and exogenic factors such as tobacco smoking and alcohol consumption (4,5). Although multiple and advanced therapeutic interventions have been developed, the majority of laryngeal cancer patients present late to hospital, which leads to reduced therapeutic efficacy and increased rate of recurrence (2). Therefore, the development of highly efficacious treatments, as well as better diagnostic and preventive measures, require a better understanding of the molecular and pathogenic mechanisms of laryngeal cancer.A disintegrins and metalloproteinases (ADAMs) are primarily located in the cell membrane, and have been shown to be involved in the proteolytic degradation of cell membrane proteins for remodelling or processing (6). Thus, ADAM family members, including ADAM10, serve pivotal roles in the pathogenesis or progression of cancers, including proliferation, angiogenesis, migration and invasion (6-9). Analysis of gene expression profiles revealed that the ADAM10 gene was significantly overexpressed in a wide variety of human malignancies, including hepatocellular carcinoma, melanoma, oral squamous cell carcinoma, lung cancer, pancreatic carcinoma, and gastric and bladder cancer (10-17). Accumulating evidence has illustrated that ADAM10 contributed to the regulation of cancer progression, chemoresistance and metastasis via the cleavage of growth factors or cell surface proteins (6,8,10,12,(18)(19)(20)(21)....

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Furin-, ADAM 10-, and γ-Secretase-Mediated Cleavage of a Receptor Tyrosine Phosphatase and Regulation of β-Catenin's Transcriptional Activity

Cited by 97 publications

References 51 publications

Receptor type protein tyrosine phosphatases (RPTPs) – roles in signal transduction and human disease

Receptor type protein tyrosine phosphatases (RPTPs) – roles in signal transduction and human disease

Receptor protein tyrosine phosphatase RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src signaling to cortactin

Clinical significance of ADAM10 expression in laryngeal carcinoma

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