Endothelial Cell-specific Chemotaxis Receptor (ECSCR) Enhances Vascular Endothelial Growth Factor (VEGF) Receptor-2/Kinase Insert Domain Receptor (KDR) Activation and Promotes Proteolysis of Internalized KDR
| Autor: | Baofeng Zhao, Ramani Ramchandran, Paula E. North, George A. Wilkinson, Sreenivasulu Kilari, Nader Rahimi, Indulekha Remadevi, Jing Pan, Robert Q. Miao, Ming You |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Indoles Angiogenesis Placenta Endosomes Biology Biochemistry Cell Line Animals Genetically Modified chemistry.chemical_compound Pregnancy parasitic diseases Human Umbilical Vein Endothelial Cells Animals Humans Pyrroles Extracellular Signal-Regulated MAP Kinases Receptor neoplasms Protein Kinase Inhibitors Molecular Biology Protein kinase B Zebrafish Vascular Endothelial Growth Factor Receptor-1 Membrane Proteins Chemotaxis Kinase insert domain receptor Tyrosine phosphorylation Cell Biology Vascular Endothelial Growth Factor Receptor-2 Molecular biology Enzyme Activation Vascular endothelial growth factor Endothelial stem cell chemistry Proteolysis cardiovascular system Female Apoptosis Regulatory Proteins Hemangioma Proto-Oncogene Proteins c-akt circulatory and respiratory physiology |
| Zdroj: | Journal of Biological Chemistry. 288:10265-10274 |
| ISSN: | 0021-9258 |
| Popis: | The endothelial cell-specific chemotaxis receptor (ECSCR) is a cell-surface protein selectively expressed by endothelial cells (ECs), with roles in EC migration, apoptosis and proliferation. Our previous study (Verma, A., Bhattacharya, R., Remadevi, I., Li, K., Pramanik, K., Samant, G. V., Horswill, M., Chun, C. Z., Zhao, B., Wang, E., Miao, R. Q., Mukhopadhyay, D., Ramchandran, R., and Wilkinson, G. A. (2010) Blood 115, 4614-4622) showed that loss of ECSCR in primary ECs reduced tyrosine phosphorylation of vascular endothelial growth factor (VEGF) receptor 2/kinase insert domain receptor (KDR) but not VEGF receptor 1/FLT1. Here, we show that ECSCR biochemically associates with KDR but not FLT1 and that the predicted ECSCR cytoplasmic and transmembrane regions can each confer association with KDR. Stimulation with VEGF165 rapidly and transiently increases ECSCR-KDR complex formation, a process blocked by the KDR tyrosine kinase inhibitor compound SU5416 or inhibitors of endosomal acidification. Triple labeling experiments show VEGF-stimulated KDR(+)/ECSCR(+) intracellular co-localization. Silencing of ECSCR disrupts VEGF-induced KDR activation and AKT and ERK phosphorylation and impairs VEGF-stimulated KDR degradation. In zebrafish, ecscr interacts with kdrl during intersomitic vessel sprouting. Human placenta and infantile hemangioma samples highly express ECSCR protein, suggesting a role for ECSCR-KDR interaction in these tissues. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|