Cell Biology and Metabolism
Mechanical Strain Induces pp60src Activation and Translocation to Cytoskeleton in Fetal Rat Lung Cells (∗)

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We have previously shown that mechanical strain-induced fetal rat lung cell proliferation is transduced via the phospholipase C-γ-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 ~110-130 kDa. Several components of this complex were identified as pp60srcsubstrates. Strain increased pp60src activity in the cytoskeletal fraction, which coincided with a shift in subcellular distribution of pp60src from the Triton-soluble to the cytoskeletal fraction. Strain-induced pp60src translocation did not appear to be mediated via the focal adhesion kinase-paxillin pathway. In contrast, strain increased the association between pp60src and the actin filament-associated protein of 110 kDa. Preincubation of cells with herbimycin A, a tyrosine kinase inhibitor, abolished strain-induced phospholipase C-γ1 tyrosine phosphorylation and its coimmunoprecipitation with pp60src. It also inhibited strain-induced DNA synthesis. These results suggest that activation of pp60src is an upstream event of the phospholipase C-γ-protein kinase C pathway that may represent an important mechanism by which mechanical perturbations are converted to biological reactions in fetal lung cells.

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This work was supported by a group grant (to M. P. and A. K. T.) and Operating Grant MT-13270 (to M. L.) from the Medical Research Council of Canada, by Grant R01HL43416 from the National Institutes of Health (to M. P.), by an operating grant (to M. L.) and equipment grants (to M. P., A. K. T., and M. L.) from the Ontario Thoracic Society, and by the Dean's Fund from the Faculty of Medicine, University of Toronto (to M. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.