Mechanical strain induces pp60(src) activation and translocation to cytoskeleton in fetal rat lung cells

We have previously shown that mechanical strain-induced fetal rat lung cell proliferation is transduced via the phospholipase C-gamma-protein kinase C pathway. In the present study, we found that protein-tyrosine kinase activity of fetal lung cells increased after a short period of strain, which was accompanied by tyrosine phosphorylation of proteins of similar to 110-130 kDa. Several components of this complex were identified as pp60(src) substrates. Strain increased pp60(src) activity in the cytoskeletal fraction, which coincided with a shift in subcellular distribution of pp60(src) hom the Triton-soluble to the cytoskeletal fraction. Strain-induced pp60(src) translocation did not appear to be mediated via the focal adhesion kinase-paxillin pathway. In contrast, strain increased the association between pp60(src) and the actin filament-associated protein of 110 kDa. Preincubation of cells with herbimycin A, a tyrosine kinase inhibitor, abolished strain-induced phospholipase C-gamma 1 tyrosine phosphorylation and its coimmunoprecipitation with pp60(src). It also inhibited strain-induced DNA synthesis. These results suggest that activation of pp60(src) is an upstream event of the phospholipase C-gamma-protein kinase C pathway that may represent an important mechanism by which mechanical perturbations are converted to biological reactions in fetal lung cells.