Mechanosensitive tyrosine phosphorylation of paxillin and focal adhesion kinase in tracheal smooth muscle

We investigatedthe role of the integrin-associated proteins focal adhesion kinase(FAK) and paxillin as mediators of mechanosensitive signal transductionin tracheal smooth muscle. In muscle strips contracted isometricallywith ACh, we observed higher levels of tyrosine phosphorylation of FAKand paxillin at the optimal muscle length(L_o) than atshorter muscle lengths of 0.5 or 0.75 L_o. Paxillinphosphorylation was also length sensitive in muscles activated byK⁺ depolarization and adjustedrapidly to changes in muscle length imposed after contractileactivation by either ACh or K⁺depolarization. Ca²⁺ depletion didnot affect the length sensitivity of paxillin and FAK phosphorylationin muscles activated with ACh, indicating that the mechanotransductionprocess can be mediated by aCa²⁺-independent pathway. SinceCa²⁺-depleted muscles do notgenerate significant active tension, this suggests that themechanotransduction mechanism is sensitive to muscle length rather thantension. We conclude that FAK and paxillin participate in anintegrin-mediated mechanotransduction process in tracheal smoothmuscle. We propose that this pathway may initiate alterations in smoothmuscle cell structure and contractility via the remodeling of actinfilaments and/or via the mechanosensitive regulation ofsignaling molecules involved in contractile protein activation.