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PMID:9299537

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Citation

Sawano, A, Takahashi, T, Yamaguchi, S and Shibuya, M (1997) The phosphorylated 1169-tyrosine containing region of flt-1 kinase (VEGFR-1) is a major binding site for PLCgamma. Biochem. Biophys. Res. Commun. 238:487-91

Abstract

Flt-1, a tyrosine kinase receptor for vascular endothelial growth factor (VEGF), plays important roles in the angiogenesis required for embryogenesis and in monocyte/macrophage migration. However, the signal transduction of Flt-1 is poorly understood due to its very weak tyrosine kinase activity. Therefore, we overexpressed Flt-1 in insect cells using the Baculovirus system in order to examine for autophosphorylation sites and association with adapter molecules such as phospholipase Cgamma-1 (PLCgamma). Tyr-1169 and Tyr-1213 on Flt-1 were found to be auto-phosphorylated, but only a phenylalanine mutant of Tyr-1169 strongly suppressed its association with PLCgamma. In Flt-1 overexpressing NIH3T3 cells, VEGF induced autophosphorylation of Flt-1, tyrosine-phosphorylation of PLCgamma and protein kinase C-dependent activation of MAP kinase. These results strongly suggest that Tyr-1169 on Flt-1 is a major binding site for PLCgamma and important for Flt-1 signal transduction within the cell.

Links

PubMed Online version:10.1006/bbrc.1997.7327

Keywords

Animals; Binding Sites; Cell Line; Humans; Isoenzymes/metabolism; Mice; Phospholipase C gamma; Phosphorylation; Receptor Protein-Tyrosine Kinases/chemistry; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Growth Factor/chemistry; Receptors, Growth Factor/metabolism; Receptors, Mitogen/chemistry; Receptors, Mitogen/metabolism; Receptors, Vascular Endothelial Growth Factor; Type C Phospholipases/metabolism; Tyrosine/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:VGFR1

involved_in

GO:0048010: vascular endothelial growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0043410: positive regulation of MAPK cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0043406: positive regulation of MAP kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0018108: peptidyl-tyrosine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

enables

GO:0005021: vascular endothelial growth factor-activated receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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