Receptor Tyrosine Phosphatase β (RPTPβ) Activity and Signaling Are Attenuated by Glycosylation and Subsequent Cell Surface Galectin-1 Binding

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 neuron-specific 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. 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 neuron-specific 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. Glycosylation is regulated spatially and temporally during the development of the nervous system (1Breen K.C. Coughlan C.M. Hayes F.D. Mol. Neurobiol. 1998; 16: 163-220Crossref PubMed Scopus (52) Google Scholar). In particular, sulfated glycoconjugates, such as the human natural killer-1 epitope, are important for proper migration and adhesion during neural development (2Schwarting G.A. Jungalwala F.B. Chou D.K. Boyer A.M. Yamamoto M. Dev. Biol. 1987; 120: 65-76Crossref PubMed Scopus (141) Google Scholar, 3Bronner-Fraser M. Dev. Biol. 1986; 115: 44-55Crossref PubMed Scopus (367) Google Scholar). The human natural killer-1 (HNK-1)3 epitope was originally discovered using a monoclonal antibody raised against a specific T-lymphoblastoid cell type (4Abo T. Balch C.M. J. Immunol. 1981; 127: 1024-1029PubMed Google Scholar). Since its discovery in lymphocytes, the HNK-1 (also known as CD57) antibody has been shown to react with many neural cell types, including glial, neuroectoderm, and neuroendocrine cells (5Lipinski M. Braham K. Caillaud J.M. Carlu C. Tursz T. J. Exp. Med. 1983; 158: 1775-1780Crossref PubMed Scopus (104) Google Scholar, 6Schuller-Petrovic S. Gebhart W. Lassmann H. Rumpold H. Kraft D. Nature. 1983; 306: 179-181Crossref PubMed Scopus (194) Google Scholar, 7Wernecke H. Lindner J. Schachner M. J. Neuroimmunol. 1985; 9: 115-130Abstract Full Text PDF PubMed Scopus (54) Google Scholar, 8Caillaud J.M. Benjelloun S. Bosq J. Braham K. Lipinski M. Cancer Res. 1984; 44: 4432-4439PubMed Google Scholar). The HNK-1 epitope consists of a glucuronic acid, transferred by glucuronyltransferases (GlcATs), that is 3-sulfated by HNK-1 sulfotransferase (HNK1st), linked to a precursor N-acetyllactosamine structure (Fig. 1). Numerous glycoproteins bearing the HNK-1 epitope have been identified in the nervous system, such as neural cell adhesion molecule (9Rathjen F.G. Wolff J.M. Frank R. Bonhoeffer F. Rutishauser U. J. Cell Biol. 1987; 104: 343-353Crossref PubMed Scopus (280) Google Scholar), L1 (10Rathjen F.G. Schachner M. EMBO J. 1984; 3: 1-10Crossref PubMed Scopus (563) Google Scholar), neural-glia cell adhesion molecule (11Grumet M. Rutishauser U. Edelman G.M. Nature. 1982; 295: 693-695Crossref PubMed Scopus (137) Google Scholar), myelin-associated glycoprotein (12McGarry R.C. Helfand S.L. Quarles R.H. Roder J.C. Nature. 1983; 306: 376-378Crossref PubMed Scopus (366) Google Scholar), tenascin R (13Woodworth A. Pesheva P. Fiete D. Baenziger J.U. J. Biol. Chem. 2004; 279: 10413-10421Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar), and RPTP (receptor protein-tyrosine phosphatase) (14Maeda N. Hamanaka H. Shintani T. Nishiwaki T. Noda M. FEBS Lett. 1994; 354: 67-70Crossref PubMed Scopus (93) Google Scholar, 15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar). In certain cell types, such as neural crest cells, the expression of the HNK-1 antigen is highly regulated during development (2Schwarting G.A. Jungalwala F.B. Chou D.K. Boyer A.M. Yamamoto M. Dev. Biol. 1987; 120: 65-76Crossref PubMed Scopus (141) Google Scholar) and is often found on migratory cells (3Bronner-Fraser M. Dev. Biol. 1986; 115: 44-55Crossref PubMed Scopus (367) Google Scholar). The HNK-1 antigen is linked to critical functions during the formation of the nervous system, such as cell-matrix interactions (16Hall H. Carbonetto S. Schachner M. J. Neurochem. 1997; 68: 544-553Crossref PubMed Scopus (71) Google Scholar), cell-cell adhesion (17Schmidt J.T. Schachner M. J. Neurobiol. 1998; 37: 659-671Crossref PubMed Scopus (26) Google Scholar), memory, and synaptic plasticity (15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar, 18Yamamoto S. Oka S. Inoue M. Shimuta M. Manabe T. Takahashi H. Miyamoto M. Asano M. Sakagami J. Sudo K. Iwakura Y. Ono K. Kawasaki T. J. Biol. Chem. 2002; 277: 27227-27231Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 19Senn C. Kutsche M. Saghatelyan A. Bosl M.R. Lohler J. Bartsch U. Morellini F. Schachner M. Mol. Cell. Neurosci. 2002; 20: 712-729Crossref PubMed Scopus (72) Google Scholar). 2The abbreviations used are: HNK-1, human natural killer-1; GlcAT, glucuronyltransferase; siRNA, short interfering RNA; PBS, phosphate-buffered saline; BSA, bovine serum albumin; WGA, wheat germ agglutinin; TBS, Tris-buffered saline; PTN, pleiotrophin; MES, 4-morpholineethanesulfonic acid; BisTris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol; LacNAc, N-acetyllactosamine; RPTP, receptor protein-tyrosine phosphatase; ERK, extracellular signal-regulated kinase. 2The abbreviations used are: HNK-1, human natural killer-1; GlcAT, glucuronyltransferase; siRNA, short interfering RNA; PBS, phosphate-buffered saline; BSA, bovine serum albumin; WGA, wheat germ agglutinin; TBS, Tris-buffered saline; PTN, pleiotrophin; MES, 4-morpholineethanesulfonic acid; BisTris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol; LacNAc, N-acetyllactosamine; RPTP, receptor protein-tyrosine phosphatase; ERK, extracellular signal-regulated kinase. The HNK-1 epitope is found on glycolipids (20Ilyas A.A. Quarles R.H. Brady R.O. Biochem. Biophys. Res. Commun. 1984; 122: 1206-1211Crossref PubMed Scopus (70) Google Scholar, 21Chou D.K. Ilyas A.A. Evans J.E. Costello C. Quarles R.H. Jungalwala F.B. J. Biol. Chem. 1986; 261: 11717-11725Abstract Full Text PDF PubMed Google Scholar), N-linked (13Woodworth A. Pesheva P. Fiete D. Baenziger J.U. J. Biol. Chem. 2004; 279: 10413-10421Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, D. M. J. Neurochem. PubMed Scopus (71) Google Scholar), and M. F. J.C. K. M. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google that a significant of the HNK-1 epitope is linked to on (15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar), which by the monoclonal antibody the antibody has been shown to react with extracellular during suggesting a for O-mannosyl-linked HNK-1 in (15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar). O-Mannosyl-linked originally to a glycosylation and J. T. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. 1981; Full Text PDF PubMed Google Scholar, W. H. T. A.M. J. Biochem. PubMed Scopus Google Scholar) the of O-mannosyl in brain in of the and and W. H. T. A.M. J. Biochem. PubMed Scopus Google Scholar, W. A.M. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). In the of O-mannosyl the that to in the is W. D. H. Biochem. J. 2002; PubMed Scopus Google Scholar), the that to the of is GnT-Vb M. M. K. W. M. M. FEBS Lett. PubMed Scopus Google Scholar), known as K. T. J. Y. S. H. H. K. N. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). shown in addition of in is GnT-Vb the K. T. J. Y. S. H. H. K. N. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). has been by and K. T. J. Y. S. H. H. K. N. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar) that the HNK-1 epitope the addition of The addition of to the of N-acetyllactosamine for the activity of glucuronyltransferases and in that to N-acetyllactosamine have been shown to important in cell adhesion and and the of GnT-Vb in C. G.A. Cell. Mol. PubMed Scopus Google Scholar). in GnT-Vb expression the levels of HNK-1 epitope found on specific neural glycoproteins and the that from expression of found that increased expression of GnT-Vb in levels of cell-cell increased and increased binding of galectin-1 to In addition, the abundant for GnT-Vb glycosylation in SH-SY5Y neuroblastoma cells was identified as a receptor protein-tyrosine phosphatase known as receptor such as which its intrinsic phosphatase activity and its to changes in cell adhesion and The on cell we GnT-Vb expression from on RPTPβ activity and signaling Our results show that GnT-Vb expression inhibits RPTPβ intrinsic phosphatase activity and its signaling phosphorylated GnT-Vb expression results in increased retention of which is the of its phosphatase activity and retention of RPTPβ receptor to increased dimerization and of phosphatase The increased retention of RPTPβ the cell is by increased with suggesting a for the of GnT-Vb glycosylation of RPTPβ and changes in neural cell adhesion and and antibody and the antibody from The antibody has been C. P. M. Hockfield S. J. Neurosci. 1997; PubMed Google Scholar, C. H. Hockfield S. J. Neurosci. 1998; PubMed Google Scholar). The antibody was from The RPTPβ antibody used K. A. T. W. M. Noda M. U. S. A. PubMed Scopus Google Scholar) was from The antibody the extracellular of RPTPβ was from The antibody and from and the antibody was from The galectin-1 antibody was from from The and from was from was from and from galectin-1 was by GnT-Vb expression was by the from K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar) the of The GnT-Vb was by the K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar) the The the of the and the from the U. P. D. R. D. PubMed Scopus Google Scholar). of and Cell and SH-SY5Y cells in with was by of cells using with the of of of and of of cell in in in The the cells with and was and was to a of and the was on cells with and the of cells was by as K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar). cell-cell cells with and in the in with for with Cell was by the of with or cells in the of and the results are expressed as a of the to the of cells and in PBS, and cell was using of in on in or in to in TBS, antibody was in and for antibody was in and for The antibody was and for the antibody was in as using and to the of cells in for addition of for in the for and of was used for of antibody was with the using of the from the and on transferred to and with the antibody The with by with antibody to for and SH-SY5Y cells in and using for to for or in TBS, with of on in and using the the cells in with in on for was by the addition of to a of for on as used in using the monoclonal RPTP antibody and SH-SY5Y cells with and from the with in with galectin-1 in PBS, for on in the of or N-acetyllactosamine in a in and in a for on the cells, on a using by the of RPTPβ SH-SY5Y cells in or N-acetyllactosamine for in PBS, bovine using the cells with antibody in a of PBS, on for The antibody was using in PBS, on for RPTPβ or GnT-Vb SH-SY5Y cells in TBS, with was from cell using and was used for of antibody was used for for was to for in and to phosphatase RPTPβ from a of was to in activity with the phosphatase using as of was used to a levels of RPTPβ by activity is shown as the of shown are the of from and on in and and The was in the and for in from the and was to a of on for by to the of was to a of and of was and the for by to GnT-Vb the of O-Mannosyl-linked HNK-1 to Cell and that of GnT-Vb or expression decreased SH-SY5Y cell migration on K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar). The that GnT-Vb and in a that O-mannosyl a in adhesion and migration of cells on laminin. In this we to for GnT-Vb that cell adhesion and The neuroblastoma cell SH-SY5Y has a neural crest the HNK-1 epitope is highly expressed in neural crest cells N. J. Neurosci. Res. PubMed Scopus Google Scholar, Baenziger J.U. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Dev. Neurosci. PubMed Scopus Google Scholar) and a in adhesion and migration to (16Hall H. Carbonetto S. Schachner M. J. Neurochem. 1997; 68: 544-553Crossref PubMed Scopus (71) Google Scholar, H. R. R. Schachner M. J. Biochem. 1997; PubMed Scopus Google Scholar). we the that GnT-Vb expression O-mannosyl-linked HNK-1 in SH-SY5Y increased GnT-Vb levels the expression of the HNK-1 epitope in SH-SY5Y cells, the cells with from a GnT-Vb expression or from by and with specific for HNK-1 and The was to glycoproteins with glycoproteins that have been by the of antibody for O-mannosyl-linked HNK-1 (15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar). Our results that the antibody a very but of in cells, and a in binding in the cells (Fig. The for and antibody binding in a (Fig. the of this glycoprotein was to N-linked or we using and by a to of using the antibody that the in this after (Fig. a of the was after that by the the with with and but the epitope was to as not The of the epitope to using that this a that the O-mannosyl-linked HNK-1 The HNK-1 epitope has been to a in cell migration during the development of the nervous system. we the of GnT-Vb expression on cell migration in to a of GnT-Vb expression migration on K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar), we the of increased GnT-Vb expression on cells on in with a and cells to for and of the cells the a of cells the with cells (Fig. the the cells have to and a the cells have the a significant of GnT-Vb expression on the of migration (Fig. we the that GnT-Vb expression cell-cell that to the HNK-1 epitope are cell adhesion of and GnT-Vb cells and as M. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). a significant of cell in the cells with cells (Fig. of the cells cell-cell cells cell or a the from a in the of cell for cells with cells (Fig. These results that GnT-Vb glycosylation cell-cell adhesion. GnT-Vb-mediated Glycosylation of RPTPβ in and in GnT-Vb glycosylation cell-cell adhesion and cell we to the glycoprotein The of the (Fig. the RPTPβ was known to the HNK-1 epitope (14Maeda N. Hamanaka H. Shintani T. Nishiwaki T. Noda M. FEBS Lett. 1994; 354: 67-70Crossref PubMed Scopus (93) Google Scholar) and in the O-mannosyl-linked HNK-1 epitope (15Dino M.R. Harroch S. Hockfield S. Matthews R.T. Neuroscience. 2006; 142: 1055-1069Crossref PubMed Scopus (58) Google Scholar). RPTPβ was using antibody and by using the we in for RPTPβ from cells with cells (Fig. levels of RPTPβ in the and GnT-Vb and by with the from that GnT-Vb expression to HNK-1 on RPTPβ that are the of expressed after GnT-Vb using from and significant of from cell type not glycosylation was on the of we the of this glycosylation on its intrinsic phosphatase activity a on RPTPβ from of cells, and cells a for the of GnT-Vb K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar). from that GnT-Vb-mediated glycosylation RPTPβ phosphatase activity by after for from (Fig. GnT-Vb expression by by the expression of the K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar). RPTPβ from GnT-Vb cells the with phosphatase activity of the by to RPTPβ in the not These results indicate that GnT-Vb-mediated glycosylation or inhibits RPTPβ this on RPTPβ phosphatase activity, we in of of this is a for and the is of RPTPβ that levels by RPTPβ phosphatase activity K. A. T. W. M. Noda M. U. S. A. PubMed Scopus Google Scholar). that the addition of O-mannosyl-linked HNK-1 to RPTPβ its phosphatase activity, after treatment with in levels for cells with cells, and of GnT-Vb this and GnT-Vb SH-SY5Y cells with for and was from cell to the levels of using the antibody from that and for in cells, cells, and GnT-Vb cells in levels after treatment with levels in to GnT-Vb expression was phosphorylated after treatment of cells with cells, GnT-Vb cells phosphorylated with cells after treatment (Fig. These results that the of RPTPβ phosphatase activity by GnT-Vb expression levels results in changes in the in of of GnT-Vb-mediated Glycosylation of RPTPβ a GnT-Vb-mediated changes in glycosylation of the extracellular of RPTPβ phosphatase activity, we the of RPTPβ and The for is on for receptor protein-tyrosine showing that of the extracellular and dimerization phosphatase activity J.T. J. W. J.M. M. J. Immunol. 2006; PubMed Scopus Google Scholar, A.M. J. T. Nature. PubMed Scopus Google Scholar). Glycosylation has been shown to the of the cell C. G.M. J. P. M. 2004; 306: PubMed Scopus Google Scholar, K. S. A. M. Cell. Full Text Full Text PDF PubMed Scopus Google we in GnT-Vb-mediated glycosylation of RPTPβ the of RPTPβ receptor on the cell to dimerization of the phosphatase the and of RPTPβ to the cell using a and found the rates to for and cells not changes in the of we with a and the cells for the with to the by RPTPβ was by using found that the RPTPβ was increased in cells with cells (Fig. The of RPTPβ the by increased of receptor with receptor during the the that GnT-Vb glycosylation was we cells with a and cell on of to in formation of RPTPβ for cells with cells (Fig. results from to RPTPβ levels on a in dimerization GnT-Vb expression (Fig. These that increased dimerization in for the increased RPTPβ levels on the cell surface. GnT-Vb expression to on glycoprotein the levels of in the structure for the of known as H. J. 1998; PubMed Scopus (26) Google Scholar). the increased of RPTPβ in cells was we the retention of the abundant in SH-SY5Y found that galectin-1 in retention to that for RPTPβ in the cells (Fig. galectin-1 and RPTPβ the cell we and using to by using RPTPβ antibody by for galectin-1 increased of galectin-1 with RPTPβ in cells with cells (Fig. found that higher levels of RPTPβ with galectin-1 in cells with cells (Fig. using a galectin-1 antibody by with RPTPβ The in retention for in the cells, with the increased of galectin-1 and that galectin-1 and RPTPβ the cell surface. These results indicate that galectin-1 binding is in for the increased retention of RPTPβ after GnT-Vb expression. galectin-1 binding to RPTPβ in cells was for the levels of the addition of for binding and RPTPβ levels to cell cell binding for galectin-1 increased after GnT-Vb expression and galectin-1 binding to SH-SY5Y cells, galectin-1 in the of or was to and SH-SY5Y cells in binding was by of cells using galectin-1 binding was in cells with cells after in (Fig. galectin-1 binding to and cells (Fig. that GnT-Vb glycosylation galectin-1 cell and that is to galectin-1 we to galectin-1 binding is to the increased retention of this we and cells in or for in the levels of cell RPTPβ by a in cell RPTPβ for cells, with cells, after (Fig. These results with of the we found that the increased cell levels of RPTPβ on cells to a cells (Fig. These results indicate that of galectin-1 binding by RPTPβ cell levels to the of results the that GnT-Vb glycosylation of RPTPβ galectin-1 resulting in receptor with increased retention and phosphatase have that expression levels of N-acetylglucosaminyltransferase neuroblastoma cell-matrix adhesion and migration on using specific for this K. M. Exp. Cell Res. 2006; PubMed Scopus Google Scholar). These shown to to changes in O-mannosyl glycan the expression of was using The results in this and show that GnT-Vb expression the levels of O-mannosyl-linked HNK-1 epitope in SH-SY5Y The HNK-1 epitope is a structure that important in neural cell adhesion and migration (3Bronner-Fraser M. Dev. Biol. 1986; 115: 44-55Crossref PubMed Scopus (367) Google Scholar) and has been shown to expressed on O-mannosyl-linked W. A.M. T. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). In this increased GnT-Vb expression to increased levels of a glycoprotein with a in cell-cell adhesion and in The antibody to a glycoprotein that O-mannosyl-linked of the of the epitope to and The that the epitope react with the HNK-1 epitope expressed on to The of GnT-Vb in SH-SY5Y cells was identified as and that GnT-Vb-mediated glycosylation RPTPβ phosphatase activity in and in was The of RPTPβ activity was by showing that β-catenin, a of RPTP has increased levels in cells treatment with cells that resulting in decreased levels of cell-cell adhesion and increased RPTPβ is in its and has been on of receptor protein-tyrosine phosphatase known as that dimerization by with the extracellular to of the A.M. J. T. Nature. PubMed Scopus Google Scholar). in particular, N-linked has been shown to the of RPTP known as in A. Immunol. 2002; 3: PubMed Scopus Google Scholar). Our that is in dimerization GnT-Vb is with the and a of with this receptor and inhibits phosphatase activity N. Noda M. J. 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Full Text Full Text PDF PubMed Scopus Google Scholar, M. R. F. P. M. M. D. M. PubMed Scopus Google Scholar, H. U. P. J. Immunol. Lett. PubMed Scopus Google Scholar). cells and neural cells are cell that These results in SH-SY5Y cells, that increased galectin-1 as a of GnT-Vb RPTPβ retention and its phosphatase a in which the O-mannosyl-linked HNK-1 N-acetyllactosamine structure that results from GnT-Vb activity galectin-1 to increased retention of RPTPβ that results in decreased activity the of receptor dimerization (Fig. or a RPTPβ is highly as a of its β-catenin, to resulting in increased levels of cell-cell adhesion (Fig. RPTPβ by GnT-Vb and the of the O-mannosyl HNK-1 galectin-1 binding and results in increased RPTPβ retention of RPTPβ receptor dimerization and changes that its intrinsic phosphatase activity, to phosphorylated levels of phosphorylated the resulting in cell-cell adhesion (Fig. and increased galectin-1 and GnT-Vb are expressed within the during are and M. Y. H. 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