The Cell Adhesion Domain in Plasma Vitronectin Is Cryptic*
- From the ‡Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037 and ¶The Burnham Institute, La Jolla, California 92037
Abstract
Vitronectin (Vn) is a major adhesive glycoprotein in blood. However, many of the functions of Vn are regulated by its conformational state and degree of multimerization. Here, the ability of native and denatured Vn to bind to integrin adhesion receptors was compared. Three lines of evidence suggest that the native, plasma form of Vn is not an adhesive glycoprotein. (i) Antibodies that bind in close proximity to the cell adhesion domain of Vn fail to bind to native Vn present in unfractionated plasma. (ii) Denatured Vn binds to both glycoprotein IIb/IIIa and αvβ3in a dose-dependent manner. In contrast, native Vn is unable to bind either integrin. (iii) Thermal denaturation of native Vn, or its complexation with type 1 plasminogen activator inhibitor, exposed the cell adhesion domain of Vn. Thus, while plasma Vn is unable to bind integrins and is not an adhesive glycoprotein, the conformationally altered from of the protein binds avidly to both αvβ3 and glycoprotein IIb/IIIa. The data presented here indicate that such conformational changes in Vn are likely to occur in areas of tissue injury and thrombosis.
Footnotes
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↵* This work was supported by Grant 4KT-0192 from the California Tobacco-related Disease Research Program (to D. S.) and by National Institutes of Health Grants HL50704 (to D. S.) and AR42750 and CA56483 (to J. W. S.). This is publication number 10379-VB from the Department of Vascular Biology.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed. Present address: DuPont Merck Research Laboratories, P. O. Box 80400, Wilmington, DE 19880-400. Tel.: 302-695-7069; Fax.: 302-695-4162; E-mail:seiffeda{at}a1.lldmpc.umc.dupont.com.
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↵‖ Established Investigator of the American Heart Association and Genentech.
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↵1 The abbreviations used are: Vn, vitronectin; GPIIb/IIIa, glycoprotein IIb/IIIa; mAb, monoclonal antibody; PAI-1, type 1 plasminogen activator inhibitor; PBS, phosphate-buffered saline; SMB, somatomedin B.
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↵2 D. Seiffert and J. W. Smith, unpublished observation.
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↵3 D. Seiffert, unpublished observation.
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- Received January 9, 1997.
- Revision received March 10, 1997.
