Depletion of focal adhesion kinase by antisense depresses contractile activation of smooth muscle

Focal adhesion kinase (FAK) undergoes tyrosine phosphorylation in response to the contractile stimulation of tracheal smooth muscle. We hypothesized t hat FAK may play an important role in signaling pathways that regulate smoo th muscle contraction. FAK antisense or FAK sense was introduced into muscl e strips by reversible permeabilization, and strips were incubated with ant isense or sense for 7 days. Antisense decreased FAK expression compared wit h that in untreated and sense-treated tissues, but it did not affect the ex pression of vinculin or myosin light chain kinase. Increases in force, intr acellular free Ca2+, and myosin light chain phosphorylation in response to stimulation with ACh or KCl were depressed in FAK-depleted tissues, but FAK depletion did not affect the activation of permeabilized tracheal muscle s trips with Ca2+. The tyrosine phosphorylation of paxillin, a substrate for FAK, was also significantly reduced in FAK-depleted strips. We conclude tha t FAK is a necessary component of the signaling pathways that regulate smoo th muscle contraction and that FAK plays a role in regulating intracellular free Ca2+ and myosin light chain phosphorylation.