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Originally published In Press as doi:10.1074/jbc.M203149200 on May 7, 2002

J. Biol. Chem., Vol. 277, Issue 27, 24835-24841, July 5, 2002
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The Selective Regulation of alpha Vbeta 1 Integrin Expression Is Based on the Hierarchical Formation of alpha V-containing Heterodimers*

Pekka KoistinenDagger § and Jyrki HeinoDagger ||

From the Dagger  MediCity Research Laboratory and the Department of Medical Biochemistry, § Turku Graduate School of Biomedical Sciences, University of Turku, FIN-20520 Turku and the  Department of Biology, University of Jyväskylä, FIN-40351 Jyväskylä, Finland

The integrin beta 1 subunit can form a heterodimer with 12 different alpha  subunits. According to the present model, the expression level of any alpha beta complex is regulated by the availability of the specific alpha  subunit, whereas beta 1 subunit is constantly present in a large excess. The expression of several heterodimers containing the alpha V subunit seems to be regulated by an identical mechanism. The fact that many cells express alpha Vbeta 1 heterodimer, and that this fibronectin/vitronectin receptor may be selectively regulated, compromises the present model of the regulation of beta 1 and alpha V integrins. We have tried to solve this problem by assuming that distinct alpha beta heterodimers are formed with different tendency. To test the hypothesis, we analyzed WM-266-4 melanoma cells transfected with a cDNA construct coding for an intracellular single-chain anti-alpha V integrin antibody. We could see 70-80% reduction in the cell surface expression of alpha V subunit. However, the only one of the alpha V integrins reduced on the cell surface was alpha Vbeta 1. This suggests that the cell surface expression level of alpha Vbeta 1 is dependent on the number of alpha V subunits available after the formation of other alpha V-containing heterodimers. Thus, there seems to be a hierarchy in the complex formation between alpha V and its different beta -partners. These observations explain how alpha Vbeta 1 can be specifically regulated without concomitant changes in the expression of other alpha V or beta 1 integrins.


* This work was supported by grants from the Academy of Finland, the Finnish Cancer Association, and the Sigrid Jusélius Foundation (Finland), and by a fellowship (to P. K.) from the Foundation for the Finnish Cancer Institute.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.

|| To whom correspondence should be addressed: Dept. of Biological and Environmental Science, University of Jyväskylä, P. O. Box 35, FIN-40351 Jyväskylä, Finland. Tel.: 358-14-2602240; Fax: 358-14-2602271; E-mail: jyrki.heino@utu.fi.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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