Publikation:

Superactivation of integrin αvβ3 by low antagonist concentrations

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2001

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Legler, Daniel F.
Wiedle, Guido
Ross, Frederick Patrick
Imhof, Beat A.

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Journal of cell science. 2001, 114(8), pp. 1545-1553. ISSN 0021-9533. eISSN 1477-9137

Zusammenfassung

Integrins are implicated in cell adhesion, migration and homeostasis. An important feature is their ability to adopt different affinity states that can be regulated by a variety of intra- and extracellular factors. To study affinity modulation of the integrin ectodomain by extracellular factors, we produced a soluble recombinant form of mouse integrin alphavbeta3 in a mammalian expression system and isolated it to purity. We show that the two transmembrane truncated integrin subunits stably associate to form a functional receptor, soluble recombinant alphavbeta3. The affinity of this receptor for its ligands vitronectin, fibronectin and fibrinogen can be modulated by the divalent cations magnesium, calcium and manganese. Most importantly, we found that a cyclic RGD-peptide has a biphasic effect on rsalphavbeta3and native purified alphavbeta3, with an antagonistic phase at high concentrations, and an agonistic phase at low concentrations. This integrin superactivation by low antagonist concentrations is shown in binding of sralphavbeta3 to immobilized ligands by ELISA, and in adhesion of cells that express the chimaeric integrin ligand KISS31 to immobilized rsalphavbeta3 and native purified alphavbeta3. Our results indicate that low concentrations of the ligand mimetic cyclo-RGD can result in superactivation of the extracellular domain of integrin alphavbeta3 to a comparable level as activation by manganese.

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570 Biowissenschaften, Biologie

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ISO 690LEGLER, Daniel F., Guido WIEDLE, Frederick Patrick ROSS, Beat A. IMHOF, 2001. Superactivation of integrin αvβ3 by low antagonist concentrations. In: Journal of cell science. 2001, 114(8), pp. 1545-1553. ISSN 0021-9533. eISSN 1477-9137
BibTex
@article{Legler2001Super-36631,
  year={2001},
  title={Superactivation of integrin αvβ3 by low antagonist concentrations},
  number={8},
  volume={114},
  issn={0021-9533},
  journal={Journal of cell science},
  pages={1545--1553},
  author={Legler, Daniel F. and Wiedle, Guido and Ross, Frederick Patrick and Imhof, Beat A.}
}
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