Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle

Adhesion to fibronectin through the alpha5 beta1 integrin enables endotheli al cells to proliferate in response to growth factors, whereas adhesion to laminin through alpha2 beta1 results in growth arrest under the same condit ions. On laminin, endothelial cells fail to translate Cyclin D1 mRNA and ac tivate CDK4 and CDK6. Activated Pac, but not MEK1, PI-3K, or Akt, rescues b iosynthesis of cyclin D1 and progression through the G(1) phase. Conversely , dominant negative Pac prevents these events on fibronectin. Mitogens prom ote activation of Pac on fibronectin but not laminin. This process is media ted by SOS and PI-3K and requires coordinate upstream signals through Shc a nd FAK. These results indicate that Pac is a crucial mediator of the integr in-specific control of cell cycle in endothelial cells.