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

Focal adhesion kinase (FAK)undergoes tyrosine phosphorylation in response to the contractilestimulation of tracheal smooth muscle. We hypothesized that FAK mayplay an important role in signaling pathways that regulate smoothmuscle contraction. FAK antisense or FAK sense was introduced intomuscle strips by reversible permeabilization, and strips were incubatedwith antisense or sense for 7 days. Antisense decreased FAK expressioncompared with that in untreated and sense-treated tissues, but it didnot affect the expression of vinculin or myosin light chain kinase. Increases in force, intracellular free Ca²⁺, and myosinlight chain phosphorylation in response to stimulation with ACh or KClwere depressed in FAK-depleted tissues, but FAK depletion did notaffect the activation of permeabilized tracheal muscle strips withCa²⁺. The tyrosine phosphorylation of paxillin, a substratefor FAK, was also significantly reduced in FAK-depleted strips. Weconclude that FAK is a necessary component of the signaling pathwaysthat regulate smooth muscle contraction and that FAK plays a role in regulating intracellular free Ca²⁺ and myosin light chain phosphorylation.