Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression

Cell proliferation is dependent upon the activation of receptor tyrosine kinases and integrins by soluble growth factors and extracellular matrix proteins, respectively. It is now apparent that concerted, rather than individual, signaling by these receptors is the critical feature responsible for cell-cycle progression through G(1) phase. ERK (extracellular signal-regulated kinase), Rho GTPases and G(1)-phase cyclin-dependent kinases are all regulated jointly by growth-factor receptors and integrins. Recent studies have begun to reveal how this regulated signaling in the cytoplasm is linked to activation of the G(1)-phase cyclin-dependent kinases in the nucleus.