β1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway.
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.
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.
Jingjing
J
Qi
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Na
N
Li
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Kun
K
Fan
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Peng
P
Yin
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Chao
C
Zhao
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.
Zengxia
Z
Li
Department of Pediatrics, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province, China.
Yi
Y
Lin
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.
Liying
L
Wang
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.
Xiliang
X
Zha
D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D004789:Enzyme Activation; D037502:Galectin 3 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D055503:Protein Multimerization; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D037502:Galectin 3; D011134:Polysaccharides; D050796:STAT3 Transcription Factor; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; C516865:PTPRT protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2