期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 21, 页码 8875-8879出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703088104
关键词
endothelial cells; ERK; fibronectin; Flk-1; Nck beta
资金
- NHLBI NIH HHS [HL43026, HL80518, R01 HL064382, P01 HL043026, HL64382, R01 HL080518] Funding Source: Medline
- NIGMS NIH HHS [GM65188, R01 GM065188] Funding Source: Medline
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 Nck beta, but shear stress did not have such an effect. SU1498 (a specific inhibitor of Flk-1) and Nck beta nm (a negative mutant of Nck beta) blocked the VEGF-induced ERK and JNK activities. Only SU1498, but not Nck beta(nm), inhibited the shearinduced ERK activity. Furthermore, neither SU1498 nor Nck beta nm 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 FIk-1 in terms of the recruitment of the adapter protein Nck beta, and they employ different components of the complex signaling network in regulating downstream molecules, e.g., ERK and JNK.
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