Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling.
Vascular endothelial (VE)-cadherin is endothelium specific, mediates homophilic adhesion, and is clustered at intercellular junctions. VE-cadherin is required for normal development of the vasculature in the embryo and for angiogenesis in the adult. Here, we report that VE-cadherin is associated with VE growth factor (VEGF) receptor-2 (VEGFR-2) on the exposure ... of endothelial cells to VEGF. The binding parallels receptor phosphorylation on tyrosine residues, which is maximal at 5 minutes and then declines within 30 minutes. Tyrosine phosphorylation of VE-cadherin was maximal at 30 minutes after the addition of the growth factor. At this time point, the protein could be coimmunoprecipitated with the adaptor protein Shc. Pull-down experiments with different Shc domains and mutants of the VE-cadherin cytoplasmic tail have shown that Shc binds to the carboxy-terminal domain of the VE-cadherin tail through its Src homology 2 domain (SH2). We found that Shc phosphorylation lasts longer in endothelial cells carrying a targeted null mutation in the VE-cadherin gene than in VE-cadherin-positive cells. These data suggest that VE-cadherin expression exerts a negative effect on Shc phosphorylation by VEGFR-2. We speculate that VE-cadherin binding to Shc promotes its dephosphorylation through associated phosphatases.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Antigens, CD, Cadherins, Cytoskeletal Proteins, Endothelial Growth Factors, Endothelium, Vascular, Humans, Lymphokines, Mutation, Phosphorylation, Proteins, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor, Receptors, Vascular Endothelial Growth Factor, Shc Signaling Adaptor Proteins, Trans-Activators, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, beta Catenin, src Homology Domains
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Antigens, CD, Cadherins, Cytoskeletal Proteins, Endothelial Growth Factors, Endothelium, Vascular, Humans, Lymphokines, Mutation, Phosphorylation, Proteins, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor, Receptors, Vascular Endothelial Growth Factor, Shc Signaling Adaptor Proteins, Trans-Activators, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, beta Catenin, src Homology Domains
Arterioscler. Thromb. Vasc. Biol.
Date: Apr. 01, 2002
PubMed ID: 11950700
View in: Pubmed Google Scholar
Download Curated Data For This Publication
9552
Switch View:
- Interactions 3