β1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway

• Published in: PloS one Vol. 9; no. 5; p. e98052
• Main Authors: Qi, Jingjing, Li, Na, Fan, Kun, Yin, Peng, Zhao, Chao, Li, Zengxia, Lin, Yi, Wang, Liying, Zha, Xiliang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2014; Public Library of Science (PLoS)
• Subjects: Biochemistry; Biology and life sciences; Catalysis; Catalytic activity; Cell adhesion & migration; Cell Line; Cell migration; Cell Movement - genetics; Cell surface; Cytokines; Dephosphorylation; Dimerization; Education; Enzyme Activation; Epidermal growth factor; Galectin 3 - metabolism; Galectin-3; Gene expression; Gene Knockdown Techniques; Glycoproteins; Glycosylation - drug effects; Humans; Immunology; Kinases; Laboratories; Medicine; Metastasis; Molecular biology; N-Acetylglucosaminyltransferase V; N-Acetylglucosaminyltransferases - genetics; N-Acetylglucosaminyltransferases - metabolism; N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase; N-glycans; Nuclei; Pancreatic cancer; Phosphatase; Phosphorylation; Polysaccharides; Polysaccharides - metabolism; Polysaccharides - pharmacology; Protein Binding; Protein Multimerization; Protein-tyrosine-phosphatase; Proteins; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - chemistry; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - metabolism; Retention; Retention time; Rodents; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Substrates; Transcription; Tyrosine; United States > US; China; Grand Island New York
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098052

Receptor-like protein tyrosine phosphatases (RPTPs) are type I transmembrane glycoproteins with N-glycans whose catalytic activities are regulated by dimerization. However, the intrinsic mechanism involved in dimerizing processes remains obscure. In this study, receptor protein tyrosine phosphatase rho (PTPRT) is identified as a novel substrate of N-Acetylglucosaminyltransferase V (GnT-V). We show that addition of β1,6 GlcNAc branches on PTPRT prolongs PTPRT's cell-surface retention time. GnT-V overexpression enhances galectin-3's cell-surface retention and promotes PTPRT's dimerization mediated by galectin-3. Increased dimerization subsequently reduces PTPRT's catalytic activity on the dephosphorylation of signal transducer and activator of transcription 3 (STAT3) at tyrosine residue 705 (pY705 STAT3), then the accumulated pY705 STAT3 translocates into the nucleus. Collectively, these findings provide an insight into the molecular mechanism by which GnT-V promotes cell migration, suggesting that accumulation of β1,6 GlcNAc branched N-glycans promotes PTPRT's dimerization and decreases its catalytic activity, resulting in enhanced cell migratory capacity.