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

We investigated the role of the integrin-associated proteins focal adhesion kinase (FAK) and paxillin as mediators of mechanosensitive signal transduc tion in tracheal smooth muscle. In muscle strips contracted isometrically w ith ACh, we observed higher levels of tyrosine phosphorylation of FAK and p axillin at the optimal muscle length (L-0) than at shorter muscle lengths o f 0.5 or 0.75 L-0. Paxillin phosphorylation was also length sensitive in mu scles activated by K+ depolarization and adjusted rapidly to changes in mus cle length imposed after contractile activation by either ACh or K+ depolar ization. Ca2+ depletion did not affect the length sensitivity of paxillin a nd FAK phosphorylation in muscles activated with ACh, indicating that the m echanotransduction process can be mediated by a Ca2+-independent pathway. S ince Ca2+ depleted muscles do not generate significant active tension, this suggests that the mechanotransduction mechanism is sensitive to muscle len gth rather than tension. We conclude that FAK and paxillin participate in a n integrin-mediated mechanotransduction process in tracheal smooth muscle. We propose that this pathway may initiate alterations in smooth muscle cell structure and contractility via the remodeling of actin filaments and/or v ia the mechanosensitive regulation of signaling molecules involved in contr actile protein activation.