TY - JOUR
T1 - The final steps of integrin activation
T2 - The end game
AU - Shattil, Sanford J.
AU - Kim, Chungho
AU - Ginsberg, Mark H.
N1 - Funding Information:
Researches quoted from our laboratories were supported by the National Institutes of Health. C.K. is the recipient of a postdoctoral fellowship from the American Institute for Cancer Research. We thank our colleagues for their understanding in cases where space limitations have forced us to cite or discuss their work less thoroughly than we would have liked to.
PY - 2010/4
Y1 - 2010/4
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.
UR - http://www.scopus.com/inward/record.url?scp=77949862490&partnerID=8YFLogxK
U2 - 10.1038/nrm2871
DO - 10.1038/nrm2871
M3 - Review article
C2 - 20308986
AN - SCOPUS:77949862490
VL - 11
SP - 288
EP - 300
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
SN - 1471-0072
IS - 4
ER -
