Tang D, Mehta D, Gunst S J
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5126, USA.
Am J Physiol. 1999 Jan;276(1):C250-8. doi: 10.1152/ajpcell.1999.276.1.C250.
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.
我们研究了整合素相关蛋白粘着斑激酶（FAK）和桩蛋白作为气管平滑肌机械敏感信号转导介质的作用。在与乙酰胆碱（ACh）等长收缩的肌条中，我们观察到，在最佳肌肉长度（Lo）时，FAK和桩蛋白的酪氨酸磷酸化水平高于较短肌肉长度（0.5或0.75 Lo）时。在由K⁺去极化激活的肌肉中，桩蛋白磷酸化也对长度敏感，并能迅速适应由ACh或K⁺去极化收缩激活后施加的肌肉长度变化。Ca²⁺耗竭并不影响用ACh激活的肌肉中桩蛋白和FAK磷酸化的长度敏感性，这表明机械转导过程可由一条不依赖Ca²⁺的途径介导。由于Ca²⁺耗竭的肌肉不会产生显著的主动张力，这表明机械转导机制对肌肉长度而非张力敏感。我们得出结论，FAK和桩蛋白参与气管平滑肌中整合素介导的机械转导过程。我们提出，该途径可能通过肌动蛋白丝的重塑和/或通过对参与收缩蛋白激活的信号分子的机械敏感调节来启动平滑肌细胞结构和收缩性的改变。
