Reference : Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 7...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/8480
Distinct involvement of beta3 integrin cytoplasmic domain tyrosine residues 747 and 759 in integrin-mediated cytoskeletal assembly and phosphotyrosine signaling.
English
Schaffner-Reckinger, Elisabeth mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Gouon, V. [> >]
Melchior, Chantal [> >]
Plançon, Sébastien mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Kieffer, N. [> >]
1998
The Journal of biological chemistry
273
20
12623-32
Yes (verified by ORBilu)
International
0021-9258
UNITED STATES
[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
[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.
http://hdl.handle.net/10993/8480

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