Selective adapter recruitment and differential signaling networks by VEGF vs. shear stress
Reads0
Chats0
TLDR
It is found that V EGF induced a rapid association of VEGF receptor 2 (Flk-1) with Nckβ, but shear stress did not have such an effect, and neither SU1498 nor Nck βnm had significant effects on the shear-induced JNK activity, which can be blocked by inhibitors of Src family kinase and ROCK kinase.Abstract:
Vascular endothelial cells are continuously exposed to mechanical and chemical stimuli, such as shear stress and VEGF, respectively. It is still not clear how cells perceive these stimuli and orchestrate their responses. Studying the molecular mechanism by which shear stress and VEGF regulate the signaling pathways in bovine endothelial aortic cells, we found that VEGF induced a rapid association of VEGF receptor 2 (Flk-1) with Nckβ, but shear stress did not have such an effect. SU1498 (a specific inhibitor of Flk-1) and Nckβnm (a negative mutant of Nckβ) blocked the VEGF-induced ERK and JNK activities. Only SU1498, but not Nckβnm, inhibited the shear-induced ERK activity. Furthermore, neither SU1498 nor Nckβnm had significant effects on the shear-induced JNK activity, which can be blocked by inhibitors of Src family kinase and ROCK kinase. Therefore, mechanical (shear stress) and chemical (VEGF) stimuli diverge at the receptor Flk-1 in terms of the recruitment of the adapter protein Nckβ, and they employ different components of the complex signaling network in regulating downstream molecules, e.g., ERK and JNK.read more
Citations
More filters
Journal ArticleDOI
Rapid signal transduction in living cells is a unique feature of mechanotransduction
Sungsoo Na,Olivier Collin,Farhan Chowdhury,Bernard Tay,Mingxing Ouyang,Yingxiao Wang,Ning Wang +6 more
TL;DR: Nanometer-scale cytoskeletal deformation analyses revealed that the strong activation sites of Src by stress colocalized with large deformation sites of microtubules, suggesting that micro Tubules are essential structures for transmitting stresses to activate cytoplasmic proteins.
Journal ArticleDOI
Fluid forces control endothelial sprouting
Jonathan W. Song,Lance L. Munn +1 more
TL;DR: It is found that fluid shear stress, such as exerted by flowing blood, attenuates EC sprouting in a nitric oxide-dependent manner and that interstitial flow,such as produced by extravasating plasma, directs endothelial morphogenesis and sprout formation.
Journal ArticleDOI
Molecular mechanisms of the vascular responses to haemodynamic forces.
TL;DR: Vascular remodelling can be allotted to a modification of the tensional strain or shear, and underlie a trend to reestablish baseline mechanical conditions, leading to functional changes within the cell.
Journal ArticleDOI
Fluorescence Proteins, Live-Cell Imaging, and Mechanobiology: Seeing Is Believing
TL;DR: This review summarizes the recent advances in FP development and imaging technologies using FPs to monitor molecular localization and activities and gene expressions in live cells and presents examples of the application of FPs and biosensors to visualize mechanotransduction events with high spatiotemporal resolutions inLive cells.
Journal ArticleDOI
Endothelial Trauma From Mechanical Thrombectomy in Acute Stroke In Vitro Live-Cell Platform With Animal Validation
Dayu Teng,Jeffrey S. Pannell,Robert C. Rennert,Jieying Li,Yi-Shuan Li,Victor W. Wong,Shu Chien,Alexander A. Khalessi +7 more
TL;DR: In vitro live-cell artificial vessel modeling enables a detailed study of the endothelium after thrombectomy and may contribute to future device design, and large animal studies confirm the relevance of this in vitro system to investigate endothelial physiology.
References
More filters
Journal ArticleDOI
Vascular endothelial growth factor (VEGF) and its receptors
TL;DR: Recent developments that have widened considerably the understanding of the mechanisms that control V EGF production and VEGF signal transduction are focused on and recent studies that have shed light on the mechanisms by which VEGf regulates angiogenesis are reviewed.
Journal ArticleDOI
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Eleni Tzima,Mohamad Irani-Tehrani,William B. Kiosses,Elizabetta Dejana,David A. Schultz,Britta Engelhardt,Gaoyuan Cao,Horace M. DeLisser,Martin A. Schwartz,Martin A. Schwartz +9 more
TL;DR: In this paper, the authors investigated the pathway upstream of integrin activation and found that PECAM-1 and VEGFR2 are sufficient to confer responsiveness to flow in heterologous cells.
Journal ArticleDOI
Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis.
TL;DR: It appears that wall shear rate may be a major controlling factor in the development of atheromatous lesions in man and in animals and a net flux of cholesterol from blood to wall cannot account for the observed normally occurring (quasi-steady state) and experimentally induced atheroma.
Journal ArticleDOI
Flow effects on prostacyclin production by cultured human endothelial cells.
TL;DR: The steady-state production rate of cells subjected to pulsatile shear stress was more than twice that of cells exposed to steadyShear stress and 16 times greater than that of Cells in stationary culture.
Journal ArticleDOI
The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1
TL;DR: In this paper, the human transcription factor Jun/AP-1 was found to be responsible for increased transcription of different cellular genes in response to tumor promoters, such as TPA, and serum factors.