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Nat Rev Mol Cell Biol. 2010 Apr;11(4):288-300. doi: 10.1038/nrm2871.

The final steps of integrin activation: the end game.

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  • 1Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.

Abstract

Cell-directed changes in the ligand-binding affinity ('activation') of integrins regulate cell adhesion and migration, extracellular matrix assembly and mechanotransduction, thereby contributing to embryonic development and diseases such as atherothrombosis and cancer. Integrin activation comprises triggering events, intermediate signalling events and, finally, the interaction of integrins with cytoplasmic regulators, which changes an integrin's affinity for its ligands. The first two events involve diverse interacting signalling pathways, whereas the final steps are immediately proximal to integrins, thus enabling integrin-focused therapeutic strategies. Recent progress provides insight into the structure of integrin transmembrane domains, and reveals how the final steps of integrin activation are mediated by integrin-binding proteins such as talins and kindlins.

PMID:
20308986
[PubMed - indexed for MEDLINE]
PMCID:
PMC3929966
Free PMC Article

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