The final steps of integrin activation: The end game

Sanford J. Shattil, Chungho Kim, Mark H. Ginsberg

Research output: Contribution to journalReview articlepeer-review

795 Citations (Scopus)


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 languageEnglish
Pages (from-to)288-300
Number of pages13
JournalNature Reviews Molecular Cell Biology
Issue number4
Publication statusPublished - 2010 Apr
Externally publishedYes

Bibliographical note

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.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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