ArticleOncogene2006
Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting SHP2 with an Active Site Inhibitor Blocks Signaling and Breast Cancer Cell Phenotypes.ACS bio & med chem Au · 2023Article
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- Strategies to overcome drug resistance using SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Review
- Article
- Adherens Junction and E-Cadherin complex regulation by epithelial polarity.Cellular and molecular life sciences : CMLS · 2016Review
- α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism.Journal of cell science · 2015Article
- Article
- The tyrosine phosphatase SHP2 regulates focal adhesion kinase to promote EGF-induced lamellipodia persistence and cell migration.Molecular cancer research : MCR · 2013Article
- Regulation of adherens junction dynamics by phosphorylation switches.Journal of signal transduction · 2012Article
- Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.American journal of physiology. Cell physiology · 2012Article
- Src homology domain 2-containing protein-tyrosine phosphatase-1 (SHP-1) binds and dephosphorylates G(alpha)-interacting, vesicle-associated protein (GIV)/Girdin and attenuates the GIV-phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway.The Journal of biological chemistry · 2011Article
- Junctional music that the nucleus hears: cell-cell contact signaling and the modulation of gene activity.Cold Spring Harbor perspectives in biology · 2009Review
- Modulation of the tumor suppressor protein alpha-catenin by ischemic microenvironment.The American journal of pathology · 2009Article
- Molecular mechanism for SHP2 in promoting HER2-induced signaling and transformation.The Journal of biological chemistry · 2009Article
- Adherens and tight junctions: structure, function and connections to the actin cytoskeleton.Biochimica et biophysica acta · 2008Review
- Bench to bedside and back again: molecular mechanisms of alpha-catenin function and roles in tumorigenesis.Seminars in cancer biology · 2008Review
- A2 isoform of mammalian translation factor eEF1A displays increased tyrosine phosphorylation and ability to interact with different signalling molecules.The international journal of biochemistry & cell biology · 2008Article
- The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury.Histology and histopathology · 2007Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Src homology 2 phosphotyrosyl phosphatase (SHP2) is a nonreceptor-type phosphatase that acts as a positive transducer of receptor Tyr kinase (RTK) signaling, particularly the Ras-REK and PI3K-Akt pathways. Recently, we have demonstrated that SHP2 is required for cell transformation induced by the constitutively active fibroblast growth factor receptor 3 (K/E-FR3) (Oncogene, 22, 6909-6918). In that study, we had detected a phosphotyrosyl protein of approximately 100 KDa (p100) in cells expressing dominant-negative SHP2 (R/E-SHP2), but its identity and relevance in SHP2-meditaed transformation was not known. Here, we report the identification of p100 as alpha-catenin, a vinculin-related protein involved in adherens junction-mediated intercellular adhesion. We show that alpha-catenin becomes Tyr phosphorylated in intercellular adhesion-dependent manner and this event is counteracted by SHP2. Substrate trapping in intact cells and immunocomplex phosphatse assays confirmed that alpha-catenin is in deed an SHP2 substrate. Tyr phosphorylation of alpha-catenin enhances its translocation to the plasma membrane and its interaction with beta-catenin, leading to enhanced actin polymerization and stabilization of adherens junction-mediated intercellular adhesion, a phenomenon commensurate with loss of the transformation phenotype. Site-directed mutagenesis studies also suggested that Tyr phosphorylation of alpha-catenin enhances its inhibitory role on cell transformation. Based on our previous work and the current report, we demonstrate that mediation of cell transformation by SHP2 is a complex process that involves modulation of the Ras-ERK and PI3K-Akt signaling pathways, intercellular adhesion, focal adhesion and actin cytoskeletal reorganization. To our knowledge, this is the first report showing regulation of alpha-catenin function by Tyr phosphorylation and its inhibitory effect on cell transformation.
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