Gudi SR, Huvar I, Taliana AP, Boss GR, Frangos JA.
FASEB J. 1997 Jul 31; 11: A1387.
Dept. of Bioengineering and Medicine, Univ. of California-San Diego, La Jolla 92093, USA.
Fluid Flow and associated shear stresses are important physical stimuli in vasoregulation, though the mechanisms behind their transduction into biochemical responses are not well understood. Activation of heterotrimeric G proteins Gq and Gi3 is a known early flow mediated response in HUVECs. Using a Photoactive nonhydrolyzable GTP analogue, azidoanilido GTP[alpha-32P] and by directly measuring Ras bound GTP and GDP, we found p21 Ras is activated transiently by fluid flow (20 dyne/cm2) within 5 sec. Flow also activated Ras in a dose dependent manner (0-20 dyne/cm2). To test the hypothesis that flow-activated heterotrimeric G proteins stimulate Ras activity, we treated HUVECs with antisense and missense oligonucleotides to G(alpha)q(20 micromolar) using lipofectin. Antisense treatment inhibited the flow induced Ras activation while missense treatment had no inhibitory effect. This indicates that flow induced Ras activation is mediated by flow stimulated Gq. These studies show that Ras is transiently activated by step changes in shear stress and that heterotrimeric G proteins mediate this signaling pathway(s).
Publication Types:
Keywords:
- Animals
- Endothelial Cells
- GTP-Binding Proteins
- Genes, ras
- Guanosine Diphosphate
- Guanosine Triphosphate
- Heterotrimeric GTP-Binding Proteins
- Humans
- Signal Transduction
- Stress, Mechanical
- genetics
Other ID:
UI: 102237284
From Meeting Abstracts