Integrin-specific activation of Rac controls progression through the G1 phase of the cell cycle

Amel Mettouchi, Sharon Klein, Wenjun Guo, Miguel Lopez-Lago, Emmanuel Lemichez, John K. Westwick, Filippo G. Giancotti

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Adhesion to fibronectin through the α5β1 integrin enables endothelial cells to proliferate in response to growth factors, whereas adhesion to laminin through α2β1 results in growth arrest under the same conditions. On laminin, endothelial cells fail to translate Cyclin D1 mRNA and activate CDK4 and CDK6. Activated Rac, but not MEK1, PI-3K, or Akt, rescues biosynthesis of cyclin D1 and progression through the G1 phase. Conversely, dominant negative Rac prevents these events on fibronectin. Mitogens promote activation of Rac on fibronectin but not laminin. This process is mediated by SOS and PI-3K and requires coordinate upstream signals through Shc and FAK. These results indicate that Rac is a crucial mediator of the integrin-specific control of cell cycle in endothelial cells.

Original languageEnglish (US)
Pages (from-to)115-127
Number of pages13
JournalMolecular Cell
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Mettouchi, A., Klein, S., Guo, W., Lopez-Lago, M., Lemichez, E., Westwick, J. K., & Giancotti, F. G. (2001). Integrin-specific activation of Rac controls progression through the G1 phase of the cell cycle. Molecular Cell, 8(1), 115-127. https://doi.org/10.1016/S1097-2765(01)00285-4