Activation of αvβ3-Vitronectin Binding Is a Multistage Process in which Increases in Bond Strength Are Dependent on Y747 and Y759 in the Cytoplasmic Domain of β3
| Autor: | David Boettiger, Scott D. Blystone, Francois Huber, Laura Lynch |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell
Cell Separation Platelet Membrane Glycoproteins Biology Ligands Transfection Article Antigens CD Cell Adhesion medicine Humans Receptors Vitronectin Vitronectin Phosphorylation Molecular Biology Process (anatomy) αvβ3 integrin Binding Sites Bond strength Integrin beta1 Integrin beta3 Cell Biology Flow Cytometry Cell biology Kinetics medicine.anatomical_structure Cytoplasm Domain (ring theory) biology.protein Tetradecanoylphorbol Acetate Stress Mechanical K562 Cells Protein Binding K562 cells |
| Zdroj: | Molecular Biology of the Cell. 12:1227-1237 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.12.5.1227 |
| Popis: | Integrin receptors serve as mechanical links between the cell and its structural environment. Using αvβ3 integrin expressed in K562 cells as a model system, the process by which the mechanical connection between αvβ3 and vitronectin develops was analyzed by measuring the resistance of these bonds to mechanical separation. Three distinct stages of activation, as defined by increases in the αvβ3-vitronectinbinding strength, were defined by mutational, biochemical, and biomechanical analyses. Activation to the low binding strength stage 1 occurs through interaction with the vitronectin ligand and leads to the phosphorylation of Y747 in the β3 subunit. Stage 2 is characterized by a 4-fold increase in binding strength and is dependent on stage1 and the phosphorylation of Y747. Stage 3 is characterized by a further 2.5-fold increase in binding strength and is dependent on stage 2 events and the availability of Y759 for interaction with cellular proteins. The Y747F mutant blocked the transition from stage 1 to stage 2, and the Y759F blocked the transition from stage 2 to stage 3. The data suggest a model for tension-induced activation of αvβ3 integrin. |
| Databáze: | OpenAIRE |
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