The final steps of integrin activation: the end game
- 1 April 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Molecular Cell Biology
- Vol. 11 (4), 288-300
- https://doi.org/10.1038/nrm2871
Abstract
Integrin activation comprises initial and intermediate signalling events and, finally, the interaction of integrins with cytoplasmic regulators such as talins and kindlins, which changes an integrin's affinity for its ligands. Targeting of these final, integrin-specific, activation events enables integrin-focused therapeutic strategies. 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.Keywords
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