Skip to main content
Article thumbnail
Location of Repository

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

By Xinchun Pi, Yaxu Wu, James E. Ferguson, Andrea L. Portbury and Cam Patterson

Abstract

The chemokine stromal cell-derived factor-1α (SDF-1α) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and endothelial cell migration, yet very little is known about the actual signaling events that mediate SDF-1α-induced endothelial cell function. In this report, we describe the identification of an intricate SDF-1α-induced signaling cascade that involves endothelial nitric oxide synthase (eNOS), JNK3, and MAPK phosphatase 7 (MKP7). We demonstrate that the SDF-1α-induced activation of JNK3, critical for endothelial cell migration, depends on the prior activation of eNOS. Specifically, activation of eNOS leads to production of NO and subsequent nitrosylation of MKP7, rendering the phosphatase inactive and unable to inhibit the activation of JNK3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for SDF-1α-induced endothelial cell migration. In addition, the discovery of this interactive network of pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases

Topics: Biological Sciences
Publisher: National Academy of Sciences
OAI identifier: oai:pubmedcentral.nih.gov:2667036
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.