Selective adapter recruitment and differential signaling networks by VEGF vs. shear stress

Yingxiao Wang, Joann Chang, Kuang Den Chen, Song Li, Julie Yi Shuan Li, Chuanyue Wu, Shu Chien*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

40 Scopus citations

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.

Original languageEnglish
Pages (from-to)8875-8879
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number21
DOIs
StatePublished - 22 05 2007
Externally publishedYes

Keywords

  • ERK
  • Endothelial cells
  • Fibronectin
  • Flk-1
  • Nckβ

Fingerprint

Dive into the research topics of 'Selective adapter recruitment and differential signaling networks by VEGF vs. shear stress'. Together they form a unique fingerprint.

Cite this