Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration

Isaji, Tomoya; Gu, Jianguo; Nishiuchi, Ryoko; Zhao, Yanyang; Takahashi, Motoko; Miyoshi, Eiji; Honke, Koichi; Sekiguchi, Kiyotoshi; Taniguchi, Naoyuki

doi:https://doi.org/10.1074/jbc.M311627200

Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration

Isaji, Tomoya; Gu, Jianguo; Nishiuchi, Ryoko et al.

Journal of Biological Chemistry, 2004, 279(19), 19747-19754

Number of Access:921（2025-08-18 14:07 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71430

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Title	Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration
Creator	NRID 1000080433514 1000080433514 CreatorName Isaji, Tomoya
	NRID 1000040260369 1000040260369 CreatorName Gu, Jianguo
	CreatorName Nishiuchi, Ryoko
	CreatorName Zhao, Yanyang
	NRID 1000000303941 1000000303941 CreatorName Takahashi, Motoko
	NRID 1000020322183 1000020322183 ORCID 0000-0002-9430-2362 0000-0002-9430-2362 researchmap permalink read0068532 read0068532 Scopus Author ID 7005784183 7005784183 CreatorName Miyoshi, Eiji
	NRID 1000080190263 1000080190263 CreatorName Honke, Koichi
	NRID 1000050187845 1000050187845 researchmap permalink read0054833 read0054833 Scopus Author ID 7201662709 7201662709 ORCID 0000-0002-6433-1410 0000-0002-6433-1410 CreatorName Sekiguchi, Kiyotoshi
	NRID 1000090002188 1000090002188 CreatorName Taniguchi, Naoyuki
Description	This research was originally published in the Journal of Biological Chemistry. Tomoya Isaji, Jianguo Gu, Ryoko Nishiuchi, Yanyang Zhao, Motoko Takahashi, Eiji Miyoshi, Koichi Honke, Kiyotoshi Sekiguchi and Naoyuki Taniguchi. Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration. J. Biol. Chem. 2004; 279: 19747-19754 © the American Society for Biochemistry and Molecular Biology
Abstract	The enzyme β1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of a bisecting GlcNAc residue to glycoproteins, resulting in a modulation in biological function. Our previous studies showed that the transfection of the GnT-III gene into B16 melanoma cells results in a suppression of invasive ability and lung colonization. The suppression has been postulated to be due to an increased level of E-cadherin expression on the cell surface, which in turn leads to the up-regulation of cell-cell adhesion. In this study, we report on the effects of overexpression of GnT-III on cell-matrix adhesion. The overexpression of GnT-III, but not that of an enzymatic inactive GnT-III (D323A), inhibits cell spreading and migration on fibronectin, a specific ligand for integrin α5β1, and the focal adhesion kinase phosphorylation. E4-PHA lectin blot analyses showed that the levels of bisecting GlcNAc structures on the integrin α5 subunit as well as α2 and α3 subunits immunoprecipitated from GnT-III transfectants were substantially increased. In addition, the affinity of the binding of integrin α5β1 to fibronectin was significantly reduced by the introduction of the bisecting GlcNAc, to the α5 subunit. These findings suggest that the modification of N-glycan of integrin by GnT-III inhibits its ligand binding ability, subsequently leading to the down-regulation of integrin-mediated signaling.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	279(19)
Page	19747-19754
Date of Issued	2004-05
Language	English
Handle URL	https://hdl.handle.net/11094/71430
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M311627200
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2004, 279(19), p. 19747-19754
DC.title	Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration
DC.creator	Isaji, Tomoya
	Gu, Jianguo
	Nishiuchi, Ryoko
	Zhao, Yanyang
	Takahashi, Motoko
	Miyoshi, Eiji
	Honke, Koichi
	Sekiguchi, Kiyotoshi
	Taniguchi, Naoyuki
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2004-05
DC.identifier	https://doi.org/10.1074/jbc.M311627200
DC.description	This research was originally published in the Journal of Biological Chemistry. Tomoya Isaji, Jianguo Gu, Ryoko Nishiuchi, Yanyang Zhao, Motoko Takahashi, Eiji Miyoshi, Koichi Honke, Kiyotoshi Sekiguchi and Naoyuki Taniguchi. Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration. J. Biol. Chem. 2004; 279: 19747-19754 © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	The enzyme β1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of a bisecting GlcNAc residue to glycoproteins, resulting in a modulation in biological function. Our previous studies showed that the transfection of the GnT-III gene into B16 melanoma cells results in a suppression of invasive ability and lung colonization. The suppression has been postulated to be due to an increased level of E-cadherin expression on the cell surface, which in turn leads to the up-regulation of cell-cell adhesion. In this study, we report on the effects of overexpression of GnT-III on cell-matrix adhesion. The overexpression of GnT-III, but not that of an enzymatic inactive GnT-III (D323A), inhibits cell spreading and migration on fibronectin, a specific ligand for integrin α5β1, and the focal adhesion kinase phosphorylation. E4-PHA lectin blot analyses showed that the levels of bisecting GlcNAc structures on the integrin α5 subunit as well as α2 and α3 subunits immunoprecipitated from GnT-III transfectants were substantially increased. In addition, the affinity of the binding of integrin α5β1 to fibronectin was significantly reduced by the introduction of the bisecting GlcNAc, to the α5 subunit. These findings suggest that the modification of N-glycan of integrin by GnT-III inhibits its ligand binding ability, subsequently leading to the down-regulation of integrin-mediated signaling.
DC.format	71430
citation_title	Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration
citation_author	Isaji, Tomoya
	Gu, Jianguo
	Nishiuchi, Ryoko
	Zhao, Yanyang
	Takahashi, Motoko
	Miyoshi, Eiji
	Honke, Koichi
	Sekiguchi, Kiyotoshi
	Taniguchi, Naoyuki
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2004-05
citation_journal_title	Journal of Biological Chemistry
citation_volume	279
citation_issue	19
citation_firstpage	19747
citation_lastpage	19754
citation_doi	https://doi.org/10.1074/jbc.M311627200
citation_public_url	https://hdl.handle.net/11094/71430

Introduction of Bisecting GlcNAc into Integrin α5β1 Reduces Ligand Binding and Down-regulates Cell Adhesion and Cell Migration

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