Phosphatidylinositol-3 kinase dependent MAP kinase activation via p21ras in endothelial cells exposed to cyclic strain.
Hemodynamic forces play a key role in the modulation of the morphology and function of the endothelium by activating several kinases. We have previously shown that cyclic strain, a repetitive mechanical stretch, induces activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), members of the mitogen activated protein (MAP) kinase family. In order to investigate the upstream pathway of strain-induced ERK1/2 activation, we examined p21ras activation by cyclic strain and the effect of wortmannin and LY294002, phosphatidylinositol-3 kinase (PI 3-kinase) inhibitors on ERK1/2 phosphorylation. Cyclic strain induced a transient and rapid activation of p21ras at 1 min after strain. Wortmannin inhibited strain-induced ERK1/2 activation by 56.3 and 86.3 %, respectively. LY294002 inhibited ERK1 activation completely and ERK2 activation by 42.9%. These results suggest a possible involvement of p21ras and PI 3-kinase in the signal transduction pathway leading to the strain-induced ERK1/2 activation.
Ikeda
M
M
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, 06510, USA.
Kito
H
H
Sumpio
B E
BE
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000378:metabolism; D006439:Hemodynamics; D009025:Morpholines / Q000494:pharmacology; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002867:Chromones; D006160:Guanosine Triphosphate; D009025:Morpholines; D015689:Oncogene Protein p21(ras); D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one