Molecular Cell
Volume 8, Issue 1, July 2001, Pages 115-127
Journal home page for Molecular Cell

Article
Integrin-Specific Activation of Rac Controls Progression through the G1 Phase of the Cell Cycle

https://doi.org/10.1016/S1097-2765(01)00285-4Get rights and content
Under an Elsevier user license
open archive

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.

Cited by (0)

6

Present address: CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France.