Fig.

5. Roles of tensins in mechanical sensing. The metabolic sensor AMPK also has a role in mechanotransduction through regulating tensins. Reduced levels of AMPK induce protein expression of TNS1 and TNS3, which bind to and activate β1 integrin activity, thereby enhancing intracellular stiffness. TNS1 is required for the stiffness-induced elongation of fibrillar adhesions. TNS1 also senses substrate stiffness by altering its protein turnover rate, which in turn modulates FAK- and Src-mediated phosphorylation events linked to cell attachment and migration. Physical stretching induces p130Cas phosphorylation by Src family kinases (SFKs), allowing TNS1 to link pTyr-p130Cas to inwardly moving actin cytoskeletons, thus promoting cell migration. Physical stretching also leads to cytoskeleton network reorganization. CTEN rapidly accumulates along tension-bearing keratin fibers, but not actin filaments in epithelial cells.