Insulin-like Growth Factor I Increases αVβ3 Affinity by Increasing the Amount of Integrin-associated Protein That Is Associated with Non-raft Domains of the Cellular Membrane

Laura A. Maile; Yumi Imai; Jane Badley Clarke; David R. Clemmons

doi:10.1074/jbc.M108380200

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Insulin-like Growth Factor I Increases αVβ3 Affinity by Increasing the Amount of Integrin-associated Protein That Is Associated with Non-raft Domains of the Cellular Membrane

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Insulin-like Growth Factor I Increases αVβ3 Affinity by Increasing the Amount of Integrin-associated Protein That Is Associated with Non-raft Domains of the Cellular Membrane

Laura A. Maile, Yumi Imai, Jane Badley Clarke and David R. Clemmons

The Journal of biological chemistry, Vol.277(3), pp.1800-1805

01/18/2002

DOI: 10.1074/jbc.M108380200

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Abstract

Insulin-like growth factor I (IGF-I) stimulates an increase in αVβ3 ligand binding. Stimulation of smooth muscle cells by IGF-I requires αVβ3 ligand occupancy, and enhanced αVβ3 ligand occupancy augments IGF-I actions. Therefore, IGF-I-induced changes in αVβ3 ligand binding may act to further enhance IGF-I actions. Integrin-associated protein (IAP) has been shown to be associated with αVβ3 and is required for the binding of αVβ3 to vitronectin-coated beads. We therefore investigated whether IGF-I could stimulate IAP-αVβ3 association resulting in enhanced ligand binding. IGF-I stimulated an increase in IAP-αVβ3 association. This was due, at least in part, to an IGF-I-stimulated redistribution of IAP from the Triton-insoluble fraction of the cell to the Triton-soluble fraction of the cell, where most of the αVβ3 was located. Inhibition of the phosphatidylinositol 3-kinase pathway blocked both the redistribution of IAP and the increase in IAP-αVβ3 association, providing further evidence that the redistribution of IAP is essential for the increase in association. An anti-IAP monoclonal antibody, blocked both the IGF-I-stimulated increase in IAP-αVβ3complex formation and cell migration. IGF-I-stimulated translocation of IAP and increase in IAP-αVβ3 association represent an important process by which IGF-I modulates αVβ3ligand binding and cellular responses.

Details

Title: Subtitle: Insulin-like Growth Factor I Increases αVβ3 Affinity by Increasing the Amount of Integrin-associated Protein That Is Associated with Non-raft Domains of the Cellular Membrane
Creators: Laura A. Maile - University of North Carolina at Chapel Hill
Yumi Imai - University of North Carolina at Chapel Hill
Jane Badley Clarke - University of North Carolina at Chapel Hill
David R. Clemmons - University of North Carolina at Chapel Hill
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(3), pp.1800-1805
DOI: 10.1074/jbc.M108380200
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 01/18/2002
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359678302771

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