2. Academic Validation
  3. β1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway

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.
Jingjing Qi 1,  Na Li 2,  Kun Fan 2,  Peng Yin 2,  Chao Zhao 2,  Zengxia Li 3,  Yi Lin 4,  Liying Wang 3,  Xiliang Zha 3
Affiliations

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.
PMID: 24846175 DOI: 10.1371/journal.pone.0098052
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.

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