Mechanical pressure-induced phosphorylation of p38 mitogen-activated protein kinase in epithelial cells via Src and protein kinase C.
Mechanical stimulation is known to modulate cell physiology in a variety of different tissues. Particularly, epithelial cells are permanently exposed to mechanical stimulation generated by externally applied forces. The present in vitro study demonstrated mechanical pressure as a trigger-factor of the p38 mitogen-activated protein kinase (MAPK) pathway in epithelial cells. Mechanical pressure applied by teflon weights (1.02g/cm(2)) led to a rapid phosphorylation of p38 peaking between 5 and 10min. Furthermore, phosphorylation of the small heat shock protein 27 (HSP27) was shown in response to mechanical pressure. Suppression of p38 function by using specific inhibitors blocked the pressure-mediated phosphorylation of HSP27. In order to identify upstream regulators of p38, a contribution of Src and protein kinase C (PKC) in pressure-signaling was investigated. We could demonstrate that inhibition of Src or PKC suppressed the pressure-induced phosphorylation of p38. These findings suggest mechanical pressure as a new type of effector stimulus for the p38 pathway with implications to (patho-) physiological conditions.
Hofmann
Matthias
M
Department of Dermatology and Venerology, University Hospital, Johann Wolfgang Goethe-University, D-60590 Frankfurt/Main, Germany.
Zaper
Julijana
J
Bernd
August
A
Bereiter-Hahn
Jürgen
J
Kaufmann
Roland
R
Kippenberger
Stefan
S
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D011138:Polytetrafluoroethylene / Q000494:pharmacology; D011312:Pressure; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases / Q000502:physiology*
D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011138:Polytetrafluoroethylene; D019061:src-Family Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases