GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:7929439

From GONUTS
Jump to: navigation, search
Citation

Waltenberger, J, Claesson-Welsh, L, Siegbahn, A, Shibuya, M and Heldin, CH (1994) Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J. Biol. Chem. 269:26988-95

Abstract

Vascular endothelial growth factor (VEGF) is a homodimeric peptide growth factor which binds to two structurally related tyrosine kinase receptors denoted Flt1 and KDR. In order to compare the signal transduction via these two receptors, the human Flt1 and KDR proteins were stably expressed in porcine aortic endothelial cells. Binding analyses using 125I-VEGF revealed Kd values of 16 pM for Flt1 and 760 pM for KDR. Cultured human umbilical vein endothelial (HUVE) cells were found to express two distinct populations of binding sites with affinities similar to those for Flt1 and KDR, respectively. The KDR expressing cells showed striking changes in cell morphology, actin reorganization and membrane ruffling, chemotaxis and mitogenicity upon VEGF stimulation, whereas Flt1 expressing cells lacked such responses. KDR was found to undergo ligand-induced autophosphorylation in intact cells, and both Flt1 and KDR were phosphorylated in vitro in response to VEGF, however, KDR much more efficiently than Flt1. Neither the receptor-associated activity of phosphatidylinositol 3'-kinase nor tyrosine phosphorylation of phospholipase C-gamma were affected by stimulation of Flt1 or KDR expressing cells, and phosphorylation of GTPase activating protein was only slightly increased. Members of the Src family such as Fyn and Yes showed an increased level of phosphorylation upon VEGF stimulation of cells expressing Flt1 but not in cells expressing KDR. The maximal responses in KDR expressing porcine aortic endothelial cells were obtained at higher VEGF concentrations as compared to HUVE cells, i.e. in the presence of Flt1. This difference could possibly be explained by the formation of heterodimeric complexes between KDR and Flt1, or other molecules, in HUVE cells.

Links

PubMed

Keywords

Actins/metabolism; Animals; Aorta/cytology; Cell Division/physiology; Cell Size/physiology; Cells, Cultured; Chemotaxis/physiology; Endothelial Growth Factors/metabolism; Endothelium, Vascular/metabolism; Lymphokines/metabolism; Organ Specificity; Phosphorylation; Proto-Oncogene Proteins/metabolism; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Growth Factor/metabolism; Receptors, Platelet-Derived Growth Factor/metabolism; Receptors, Vascular Endothelial Growth Factor; Recombinant Proteins/metabolism; Signal Transduction; Swine; Umbilical Veins/cytology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors

Significance

Annotations

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

HUMAN:VEGFA

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:VEGFA

involved_in

GO:0050927: positive regulation of positive chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0008360: regulation of cell shape

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VEGFA

involved_in

GO:0030949: positive regulation of vascular endothelial growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR2

involved_in

GO:0050927: positive regulation of positive chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR2

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR2

involved_in

GO:0008360: regulation of cell shape

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR2

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.