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Ligand-dependent activation of integrin alpha vbeta 3
Boyd Butler1, Matthew P Williams, Scott D Blystone
1Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
The Journal of Biological Chemistry
|November 26, 2002
Summary
Leukocyte adhesion receptor alpha(v)beta(3) uses distinct signaling pathways to bind vitronectin versus fibronectin. This allows immune cells to adapt migration strategies for effective immune surveillance.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Leukocyte adhesion and migration are crucial for immune surveillance.
- Integrin receptors, like alpha(v)beta(3), regulate leukocyte adhesion.
- Understanding integrin activation mechanisms is key to immune cell function.
Purpose of the Study:
- To investigate the distinct signaling pathways for alpha(v)beta(3) integrin activation.
- To compare alpha(v)beta(3) activation upon binding to vitronectin versus fibronectin.
Main Methods:
- Utilized K562 cells stably expressing alpha(v)beta(3).
- Examined tyrosine phosphorylation of the beta(3) subunit.
- Assessed the roles of phosphoinositide 3-kinase, protein kinase C, Syk, and Rho.
Main Results:
- Adhesion to vitronectin required beta(3) tyrosine phosphorylation and activation of PI3K and PKC.
- Adhesion to fibronectin occurred without beta(3) tyrosine phosphorylation, PI3K, or PKC.
- Both ligands required Syk and Rho activity for firm adhesion and actin stress fiber formation.
Conclusions:
- Alpha(v)beta(3) integrin employs unique signaling pathways depending on the extracellular matrix ligand.
- Distinct signaling enables tailored cellular responses for immune cell migration and function.
- This explains the observed 'promiscuous' ligand specificity of integrins.
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