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.
| Original language | English |
|---|---|
| Pages (from-to) | 288-300 |
| Number of pages | 13 |
| Journal | Nature Reviews Molecular Cell Biology |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2010 Apr 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
The final steps of integrin activation : The end game. / Shattil, Sanford J.; Kim, Chungho; Ginsberg, Mark H.
In: Nature Reviews Molecular Cell Biology, Vol. 11, No. 4, 01.04.2010, p. 288-300.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The final steps of integrin activation
T2 - The end game
AU - Shattil, Sanford J.
AU - Kim, Chungho
AU - Ginsberg, Mark H.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrm2871
DO - 10.1038/nrm2871
M3 - Article
VL - 11
SP - 288
EP - 300
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
SN - 1471-0072
IS - 4
ER -