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 transduction in tracheal smooth muscle. In muscle strips contracted isometrically with ACh, we observed higher levels of tyrosine phosphorylation of FAK and paxillin at the optimal muscle length (Lo) than at shorter muscle lengths of 0.5 or 0.75 Lo. Paxillin phosphorylation was also length sensitive in muscles activated by K+ depolarization and adjusted rapidly to changes in muscle length imposed after contractile activation by either ACh or K+ depolarization. Ca2+ depletion did not affect the length sensitivity of paxillin and FAK phosphorylation in muscles activated with ACh, indicating that the mechanotransduction process can be mediated by a Ca2+-independent pathway. Since Ca2+-depleted muscles do not generate significant active tension, this suggests that the mechanotransduction mechanism is sensitive to muscle length rather than tension. We conclude that FAK and paxillin participate in an 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 via the mechanosensitive regulation of signaling molecules involved in contractile protein activation.
Tang
D
D
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5126, USA.
Mehta
D
D
Gunst
S J
SJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D051416:Focal Adhesion Protein-Tyrosine Kinases; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012016:Reference Values; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; D014443:Tyrosine; D011189:Potassium Chloride; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000109:Acetylcholine