Receptor tyrosine phosphatase β (RPTPβ) activity and signaling are attenuated by glycosylation and subsequent cell surface galectin-1 binding Article

Abbott, KL, Matthews, RT, Pierce, M. (2008). Receptor tyrosine phosphatase β (RPTPβ) activity and signaling are attenuated by glycosylation and subsequent cell surface galectin-1 binding . JOURNAL OF BIOLOGICAL CHEMISTRY, 283(48), 33026-33035. 10.1074/jbc.M803646200

cited authors

  • Abbott, KL; Matthews, RT; Pierce, M

authors

abstract

  • O-Mannosyl-linked glycosylation is abundant within the central nervous system, yet very few glycoproteins with this glycan modification have been identified. Congenital diseases with significant neurological defects arise from inactivating mutations found within the glycosyltransferases that act early in the O-mannosyl glycosylation pathway. The N-acetylglucosaminyltransferase known as GnT-Vb or -IX is highly expressed in brain and branches O-mannosyl-linked glycans. Our results using SH-SY5Y neuroblastoma cells indicate that GnT-Vb activity promotes the addition of the O-mannosyl-linked HNK-1 modification found on the developmentally regulated and neuronspecific receptor protein-tyrosine phosphatase β (RPTPβ). These changes in glycosylation accompany decreased cell-cell adhesion and increased rates of migration on laminin. In addition, we show that expression of GnT-Vb promotes its dimerization and inhibits RPTPβ intrinsic phosphatase activity, resulting in higher levels of phosphorylated β-catenin, suggesting a mechanism by which GnT-Vb glycosylation couples to changes in cell adhesion. GnT-Vb-mediated glycosylation of RPTPβ promotes galectin-1 binding and RPTPβ levels of retention on the cell surface. N-Acetyllactosamine, but not sucrose, treatment of cells results in decreased RPTP retention, showing that galectin-1 binding contributes to the increased retention after GnT-Vb expression. These results place GnT-Vb as a regulator of RPTPβ signaling that influences cell-cell and cell-matrix interactions in the developing nervous system. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

publication date

  • November 28, 2008

published in

Digital Object Identifier (DOI)

start page

  • 33026

end page

  • 33035

volume

  • 283

issue

  • 48