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PMID:11312102

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Citation

Huang, K, Andersson, C, Roomans, GM, Ito, N and Claesson-Welsh, L (2001) Signaling properties of VEGF receptor-1 and -2 homo- and heterodimers. Int. J. Biochem. Cell Biol. 33:315-24

Abstract

Vascular endothelial growth factor (VEGF-A) exerts its effects through receptor tyrosine kinases VEGF receptor-1 (VEGFR-1) and VEGFR-2, which are expressed on most endothelial cell types in vitro and in vivo. We have examined VEGF-A-induced signal transduction in porcine aortic endothelial (PAE) cells individually expressing VEGFR-1 or VEGFR-2, and cells co-expressing both receptor types. We show that VEGF-A-stimulated PAE cells co-expressing VEGFR-1 and -2 contain receptor heterodimers. VEGF-A-stimulation of all three cell lines (expressing VEGFR-1, -2 and -1/2) resulted in signal transduction with different efficiencies. Thus, tyrosine phosphorylation of phospholipase Cgamma, and accumulation of inositol polyphosphates were efficiently transduced in the VEGFR-1/2 cells whereas cells expressing VEGFR-1 responded poorly in these assays. In contrast, VEGF-A-induced activation of phosphoinositide 3-kinase and induction of Ca2+ fluxes were transduced well by VEGFR-1 and VEGFR-2 homo- and heterodimers. The pattern of Ca2+ fluxes was unique for each type of VEGF receptor dimer. Our data show that signal transduction induced by VEGF-A is transduced in distinct manners by homo- and heterodimers of VEGF receptors.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Cell Line; Dimerization; Endothelium, Vascular/cytology; Endothelium, Vascular/metabolism; Enzyme Activation; Inositol Phosphates/metabolism; Isoenzymes/metabolism; Molecular Sequence Data; Phosphatidylinositol 3-Kinases/metabolism; Phospholipase C gamma; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/metabolism; Receptor Protein-Tyrosine Kinases/chemistry; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Growth Factor/chemistry; Receptors, Growth Factor/metabolism; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Substrate Specificity; Swine; Type C Phospholipases/metabolism; Vascular Endothelial Growth Factor Receptor-1

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:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0043552: positive regulation of phosphatidylinositol 3-kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

involved_in

GO:0010863: positive regulation of phospholipase C activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VGFR1

enables

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

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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