Rapid Activation of Ras by Fluid Flow Is Mediated by Gα
            <sub>q</sub>
            and Gβγ Subunits of Heterotrimeric G Proteins in Human Endothelial Cells

Gudi, Sivaramaprasad; Huvar, Ivana; White, Charles R.; McKnight, Nathan L.; Dusserre, Nathalie; Boss, Gerry R.; Frangos, John A.

doi:10.1161/01.atv.0000073314.51987.84

Cited by 63 publications

(48 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activation may be even more extensive as recently shear was shown to have downstream effects that required Gα(q) and Gβγ to activate Ras itself (Gudi et al, 2003). While this specific activation has not been shown in bone cells, as we have stated, mechanically responsive systems appear to be somewhat universal with regard to cells and are likely to be true for osteoblasts and osteocytes.…”

Section: Signaling Through G-proteinsmentioning

confidence: 66%

“…In essence, mechanical forces have been shown to activate every type of signal transduction cascade, from increases in intracellular cAMP (Lavandero et al, 1993), IP3 and intracellular calcium (Dassouli et al, 1993;Li et al, 2004), guanine regulatory proteins (Gudi et al, 2003), and MAPK (Rubin et al, 2002c). As previously stated, this review does not aim to collect each and every report of each signal cascade stimulated by mechanical force in bone cells.…”

Section: Mechanically Activated Intracellular Signaling Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

View full text Add to dashboard Cite

Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

show abstract

Section: Signaling Through G-proteinsmentioning

confidence: 66%

Section: Mechanically Activated Intracellular Signaling Systemsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

View full text Add to dashboard Cite

show abstract

“…The shear-stress-induced tyrosine phosphorylation of PECAM-1 is a delayed phenomenon relative to the activation of Ras (Gudi et al, 2003) or of K + channels (Olesen et al, 1988) and the fact that a tyrosine kinase must be activated in order for PECAM-1 to be phosphorylated means it is unlikely that PECAM-1 acts as a mechanoreceptor per se. Indeed, fluid shear stress elicits the tyrosine phosphorylation of PECAM-1 mutants that lack the transmembrane domain of the adhesion molecule and that do not localize to the lateral membranes or participate in cell-cell homophilic PECAM-1 binding (Kaufman et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells

Fleming

Fißlthaler

Dixit

et al. 2005

Journal of Cell Science

283

245

View full text Add to dashboard Cite

PP1 the phosphorylation of AMPK was unaffected. Downregulation of PECAM-1 using a siRNA approach attenuated the shear-stress-induced phosphorylation of Akt and eNOS, as well as the shear-stress-induced accumulation of cyclic GMP levels while the shear-stressinduced phosphorylation of AMPK remained intact. A comparable attenuation of Akt and eNOS (but not AMPK) phosphorylation and NO production was also observed in endothelial cells generated from PECAM-1-deficient mice.These data indicate that the shear-stress-induced activation of Akt and eNOS in endothelial cells is modulated by the tyrosine phosphorylation of PECAM-1 whereas the shear-stress-induced phosphorylation of AMPK is controlled by an alternative signaling pathway.

show abstract

“…Treatment of endothelial cells with anti-sense G q oligonucleotides inhibits shear stress-induced Ras-GTPase activity, while the transfection of G 1 2 enhances the shear stress-induced Ras activation [78]. It has also been reported that the shear stress-mediated activation of ERK1/2 is abolished by the treatment of endothelial cells with the G i inhibitor pertussis toxin [79].…”

Section: G-protein-coupled Receptors (Gpcrs) and G Proteinsmentioning

confidence: 99%

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

Ngai¹

2012

TOCVJ

View full text Add to dashboard Cite

Shear stress, the frictional drag on the endothelium from blood flow, is a major determinant of vascular physiology and pathology. Due to the pulsatile nature of blood flow, blood vessels are subjected to significant variations in mechanical forces. Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in detecting and responding to the mechanical forces generated by shear stress. Multiple sensing mechanisms are used by endothelial cells to detect changes in mechanical forces, leading to the activation of signaling networks. This review attempts to bring together recent findings on the mechanosensors present in the endothelial cells, and the regulation of endothelium-derived vasoactive autacoid production by shear stress.

show abstract

Rapid Activation of Ras by Fluid Flow Is Mediated by Gα _q and Gβγ Subunits of Heterotrimeric G Proteins in Human Endothelial Cells

Abstract: These results suggest that the rapid, shear-induced activation of Ras is mediated by Galpha(q) through the activity of Gbetagamma subunits in human vascular endothelial cells.

Cited by 63 publications

References 43 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

Contact Info

Product

Resources

About

Rapid Activation of Ras by Fluid Flow Is Mediated by Gα q and Gβγ Subunits of Heterotrimeric G Proteins in Human Endothelial Cells

Abstract: These results suggest that the rapid, shear-induced activation of Ras is mediated by Galpha(q) through the activity of Gbetagamma subunits in human vascular endothelial cells.

Cited by 63 publications

References 43 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

Contact Info

Product

Resources

About

Rapid Activation of Ras by Fluid Flow Is Mediated by Gα _q and Gβγ Subunits of Heterotrimeric G Proteins in Human Endothelial Cells