β1,6 GlcNAc branches-modified protein tyrosine phosphatase Mu attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways.

Abstract

The metastatic potential of malignant tumor has been shown to be correlated with the increased expression of tri- and tetra-antennary β1,6-N-acetylglucosamine (β1,6-GlcNAc) N-glycans. In this study, We found that GnT-V expression was negatively correlated with receptor protein tyrosine phosphatase type μ(RPTPμ) in human glioma tissues. To study whether RPTPμ is a novel substance of GnT-V which further affect RPTPμ's downstream dephosphorylation function, we preform lentiviral infection with GnT-V gene to construct stably transfected GnT-V glial cell lines. We found RPTPμ undergone severer cleavage in GnT-V transfected glioma cells compare to Mock cells. RPTPμ intracellular domain fragments increased while β1,6-GlcNAc-branched N-glycans increased, in consistent with the decrease of RPTPμ's catalytic activity. The results showed that abnormal glycosylation could decrease the phosphorylation activity of PTP μ, and affect PLCγ-PKC pathways. Both protease inhibitor Furin and N-glycan biosynthesis inhibitor swainsonine could decrease cell mobility in GnT-V-U87 transfectants and other glioma cell lines. All results above suggest increased post-translational modification of RPTPμ N-glycans by GnT-V attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways, and that the β1,6-GlcNAc-branched N-glycans of RPTPμ play a crucial role in glioma invasivity.

• Authors: Yan Gao, Fuming Yang, Zuopeng Su, Zijian He, Jin Xiao, Yaolin Xu, Xiliang Zha, Fulin Xu, Liying Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 505 Issue 2 Pg. 569-577 (10 28 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 30274773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• beta-Glucans
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
• Protein Kinase C
• PTPRM protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 2
• Phospholipase C gamma

Topics

• Cell Movement
• Focal Adhesions
• Glioma (enzymology, physiopathology)
• Glycosylation
• Humans
• N-Acetylglucosaminyltransferases (metabolism)
• Phospholipase C gamma (metabolism)
• Protein Kinase C (metabolism)
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (metabolism)
• Signal Transduction
• beta-Glucans (metabolism)