Fig. 1. A schematic diagram of how forces applied via the ECM (A) or directly to the cell surface (B) travel to integrin-anchored focal adhesions through matrix attachments or cytoskeletal filaments, respectively. Internally generated tension and forces transmitted via cell-cell contact similarly reach focal adhesions through the cytoskeleton. Forces concentrated within the focal adhesion (magnified at bottom of the figure) can stimulate clustering of dimeric (,ß) integrin receptors and induce recruitment of focal adhesion proteins [e.g. Vinculin (Vin), Paxillin (Pax), Talin (Tal)] that connect directly to microfilaments and indirectly to microtubules and intermediate filaments (certain integrins can also connect directly to intermediate filaments, for example, within hemidesmosomes). Forces applied to this specialized cytoskeletal adhesion complex activate integrin-associated signaling cascades, which among others, include such protein as focal adhesion kinase (FAK), extracellular signal-regulated protein kinase (ERK), Shc, Rho, mDia1, caveolin-1 (cav-1), CD47, heterotrimeric G-proteins, adenylate cyclase (AC) and protein kinase A (PKA).