The stretch imposed on the vascular wall by the blood pressure is important for maintenance of a contractile phenotype of the vascular smooth muscle cells. Stretch of intact mouse portal vein smooth muscle in vitro activates Rho, which increases actin polymerization and contractile protein synthesis (Albinsson et al. J Biol Chem 279:34849, 2004). Stretch also increases ERK1/2 phosphorylation with a peak at a much earlier timepoint than Rho activation (5 min vs. 24 h). We studied the effects of stretch on integrin activation in portal veins by measurement of focal adhesion kinase (FAK) phosphorylation. When phosphorylated, FAK is able to activate downstream signalling molecules, such as MAP-kinases and PI3-kinase, which are known to promote protein synthesis and proliferation. We found that FAK phosphorylation in response to stretch is biphasic with peaks at both 15 min and 24-72 h. The early phosphorylation of FAK coincides with the rapid activation of ERK1/2 while the late response could be involved in activation of Rho. Integrins and FAK are closely linked to the actin cytoskeleton, and the formation of focal adhesions is likely to depend on a

redistribution of actin filaments. Stabilization of actin filaments with jasplakinolide (24-72 h) was found to inhibit stretch-induced FAK phosphorylation in the portal vein. In contrast, basal ERK1/2 signaling was surprisingly activated by stabilization of actin filaments, which also resulted in increased protein synthesis. These results indicate that the state of the actin cytoskeleton differentially regulates several intracellular signalling events regulating growth and differentiation.