Mechanical strain induces pp60src 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 approximately 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-gamma1 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-gamma-protein kinase C pathway that may represent an important mechanism by which mechanical perturbations are converted to biological reactions in fetal lung cells.
Liu
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Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, Department of Pediatrics, University of Toronto, Toronto M5G 1X8, Canada.
Qin
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Liu
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Tanswell
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D000818:Animals; D001692:Biological Transport; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011247:Pregnancy; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007527:Isoenzymes; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D010738:Type C Phospholipases; D051966:Phospholipase C gamma