Reference : Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 7...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/10993/8480

Title :	Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 759 in integrin-mediated cytoskeletal assembly and phosphotyrosine signaling.
Language :	English
Author, co-author :	Schaffner-Reckinger, Elisabeth [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
	Gouon, V. [> >]
	Melchior, Chantal [> >]
	Plançon, Sébastien [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
	Kieffer, N. [> >]
Publication date :	1998
Journal title :	The Journal of biological chemistry
Volume :	273
Issue/season :	20
Pages :	12623-32
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	0021-9258
Country :	UNITED STATES
Keywords :	[en] Amino Acid Sequence ; Animals ; Antigens, CD/chemistry/metabolism ; CHO Cells ; Cell Adhesion Molecules/metabolism ; Cell Movement ; Cricetinae ; Cytoplasm/metabolism ; Cytoskeleton/metabolism ; Fibrinogen/metabolism ; Focal Adhesion Protein-Tyrosine Kinases ; Integrin beta3 ; Molecular Sequence Data ; Phosphorylation ; Phosphotyrosine/metabolism ; Platelet Membrane Glycoproteins/chemistry/metabolism ; Protein-Tyrosine Kinases/metabolism ; Sequence Homology, Amino Acid ; Signal Transduction
Abstract :	[en] We have investigated the structural requirements of the beta3 integrin subunit cytoplasmic domain necessary for tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin during alphav beta3-mediated cell spreading. Using CHO cells transfected with various beta3 mutants, we demonstrate a close correlation between alphav beta3-mediated cell spreading and tyrosine phosphorylation of FAK and paxillin, and highlight a distinct involvement of the NPLY747 and NITY759 motifs in these signaling processes. Deletion of the NITY759 motif alone was sufficient to completely prevent alphav beta3-dependent focal contact formation, cell spreading, and FAK/paxillin phosphorylation. The single Y759A substitution induced a strong inhibitory phenotype, while the more conservative, but still phosphorylation-defective, Y759F mutation restored wild type receptor function. Alanine substitution of the highly conserved Tyr747 completely abolished alphav beta3-dependent formation of focal adhesion plaques, cell spreading, and FAK/paxillin phosphorylation, whereas a Y747F substitution only partially restored these events. As none of these mutations affected receptor-ligand interaction, our results suggest that the structural integrity of the NITY759 motif, rather than the phosphorylation status of Tyr759 is important for beta3-mediated cytoskeleton reorganization and tyrosine phosphorylation of FAK and paxillin, while the presence of Tyr at residue 747 within the NPLY747 motif is required for optimal beta3 post-ligand binding events.
Permalink :	http://hdl.handle.net/10993/8480

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