Identification of Vascular Endothelial Growth Factor Receptor-1 Tyrosine Phosphorylation Sites and Binding of SH2 Domain-containing Molecules
| Autor: | Christer Wernstedt, Lena Claesson-Welsh, Nobuyuki Ito, Ulla Engström |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Phosphopeptides SH2 Domain-Containing Protein Tyrosine Phosphatases Swine Protein Tyrosine Phosphatase Non-Receptor Type 11 Peptide Mapping Biochemistry Receptor tyrosine kinase src Homology Domains Mice chemistry.chemical_compound Cell surface receptor Proto-Oncogene Proteins Animals Humans Growth factor receptor inhibitor Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Binding Sites Vascular Endothelial Growth Factor Receptor-1 biology Chemistry Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins Proteins Receptor Protein-Tyrosine Kinases Tyrosine phosphorylation 3T3 Cells Cell Biology Peptide Fragments Recombinant Proteins Cell biology Vascular endothelial growth factor B Vascular endothelial growth factor A Vascular endothelial growth factor C Type C Phospholipases biology.protein Tyrosine Endothelium Vascular GRB2 Protein Tyrosine Phosphatases Baculoviridae Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 273:23410-23418 |
| ISSN: | 0021-9258 |
| Popis: | Receptor tyrosine phosphorylation is crucial for signal transduction by creating high affinity binding sites for Src homology 2 domain-containing molecules. By expressing the intracellular domain of Flt-1/vascular endothelial growth factor receptor-1 in the baculosystem, we identified two major tyrosine phosphorylation sites at Tyr-1213 and Tyr-1242 and two minor tyrosine phosphorylation sites at Tyr-1327 and Tyr-1333 in this receptor. This pattern of phosphorylation of Flt-1 was also detected in vascular endothelial growth factor-stimulated cells expressing intact Flt-1. In vitro protein binding studies using synthetic peptides and immunoblotting showed that phospholipase C-gamma binds to both Y(p)1213 and Y(p)1333, whereas Grb2 and SH2-containing tyrosine protein phosphatase (SHP-2) bind to Y(p)1213, and Nck and Crk bind to Y(p)1333 in a phosphotyrosine-dependent manner. In addition, unidentified proteins with molecular masses around 74 and 27 kDa bound to Y(p)1213 and another of 75 kDa bound to Y(p)1333 in a phosphotyrosine-dependent manner. SHP-2, phospholipase C-gamma, and Grb2 could also be shown to bind to the intact Flt-1 intracellular domain. These results indicate that a spectrum of already known as well as novel phosphotyrosine-binding molecules are involved in signal transduction by Flt-1. |
| Databáze: | OpenAIRE |
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