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Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1997 Nov 26; Vol. 240 (3), pp. 635-9. - Publication Year :
- 1997
-
Abstract
- Vascular endothelial cell growth factor interacts with the receptor tyrosine kinases Flt-1 and KDR/Flk-1. We report that both receptors bind to PLC gamma and display specificity for the N-SH2 over the C-SH2 domain. Extensive site-directed mutagenesis of Flt-1 reveals that the juxta-membrane Y794, and the carboxyl terminal Y1169, are two major sites of interaction. Amino acids in the +1, +2 and +3 positions following these tyrosines are LSI and IPI, respectively. Peptide maps generated from wild type and mutant Flt-1 confirms that these residues are autophosphorylated. As predicted, mutagenesis of the analogous amino acids in KDR, positions Y801F and Y1175F, which lie in contexts YLSI and YIVL, respectively, reduced interactions of PLC gamma with this receptor. We conclude that both Flt-1 and KDR have the potential to signal through PLC gamma via phosphotyrosine residues located in juxta-membrane and carboxyl tail regions.
- Subjects :
- Amino Acid Sequence
Binding Sites
Blotting, Western
Chromatography, High Pressure Liquid
DNA Mutational Analysis
Isoenzymes chemistry
Molecular Sequence Data
Mutagenesis, Site-Directed
Oligodeoxyribonucleotides chemistry
Peptide Mapping
Phospholipase C gamma
Phosphorylation
Phosphotyrosine metabolism
Protein Binding
Proto-Oncogene Proteins chemistry
Proto-Oncogene Proteins genetics
Receptor Protein-Tyrosine Kinases chemistry
Receptor Protein-Tyrosine Kinases genetics
Receptors, Growth Factor genetics
Receptors, Vascular Endothelial Growth Factor
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Trypsin metabolism
Type C Phospholipases chemistry
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
src Homology Domains
Endothelial Growth Factors metabolism
Isoenzymes metabolism
Lymphokines metabolism
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Receptors, Growth Factor metabolism
Type C Phospholipases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 240
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 9398617
- Full Text :
- https://doi.org/10.1006/bbrc.1997.7719