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

Jingjing Qi; Na Li; Kun Fan; Peng Yin; Chao Zhao; Zengxia Li; Yi Lin; Liying Wang; Xiliang Zha

doi:10.1371/journal.pone.0098052

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

PLoS One. 2014 May 20;9(5):e98052. doi: 10.1371/journal.pone.0098052. eCollection 2014.

Authors

Jingjing Qi¹, Na Li², Kun Fan², Peng Yin², Chao Zhao², Zengxia Li³, Yi Lin⁴, Liying Wang³, Xiliang Zha³

Affiliations

¹ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China.
² Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Key Laboratory of Glycoconjugate Research, Ministry of Health, Shanghai, China; Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai, China.
⁴ Department of Pediatrics, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Movement* / genetics
Enzyme Activation
Galectin 3 / metabolism
Gene Knockdown Techniques
Glycosylation / drug effects
Humans
N-Acetylglucosaminyltransferases / genetics
N-Acetylglucosaminyltransferases / metabolism
Polysaccharides / metabolism
Polysaccharides / pharmacology
Protein Binding
Protein Multimerization
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Signal Transduction*

Substances

Galectin 3
Polysaccharides
STAT3 Transcription Factor
N-Acetylglucosaminyltransferases
alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
PTPRT protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 2

Grants and funding

This work was supported by the following grant sponsors: National Basic Research Program of China (2012CB822104), National Natural Science Foundation of China (Nos. 31070721, 81000873, 31370809). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.