Fig. 1. Integrin/RTK synergies that regulate cell cycle progression. Integrins enhance activation of RTKs by their growth factor (GF) ligands and enhance transmission of the signal to ERK at multiple points. Integrins both directly activate and enhance growth factor activation of Rac and Cdc42 through an effect on membrane targeting. Integrins contribute to activation of PI3K, possibly via FAK and Cdc42, and promote polymerization and organization of actin filaments through both direct physical connections (that are not displayed) and a variety of signaling pathways. Integrin interactions with caveolin and Shc also contribute to cell cycle progression, although whether this is due to Ras/ERK or unknown pathways is unclear. Note that many signaling events such as Raf/MEK/ERK and Akt activation occur on the membrane even though they are drawn in the cytoplasm to avoid overcrowding.