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Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor.
- Source :
-
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research [Cell Growth Differ] 1996 Feb; Vol. 7 (2), pp. 213-21. - Publication Year :
- 1996
-
Abstract
- Placenta Growth Factor (PIGF) is a new member of vascular endothelial growth factor (VEGF) family. Although VEGF binds Flt family Flt-1 and KDR/Flk-1 tyrosine kinases at high affinity for signal transduction, biological activities and the receptors of PIGF have not been extensively studied. Reverse transcription-PCR showed that PIGF-2, a subtype of PIGF-1 that bears a basic amino acid-rich domain, is more abundant than PIGF-1 and thus is the major subtype in human placenta. Using antibodies specific to PIGF-1 or -2 as markers, we obtained large amounts of PIGFs in the baculovirus expression system. PIGF-2 had growth-stimulatory activity on human umbilical vein endothelial cells and vascular permeability activity in the Miles assay at levels about 10-fold lower than those of VEGF. All PIGF-1 activities were lower than those of PIGF-2. Both PIGFs competed for the binding of 125I-labeled VEGF to Flt-1 receptor but not to KDR/Flk-1 expressed on NIH3T3 cells. Furthermore, 125I-labeled PIGF bound to Flt-1 at high affinity but not to KDR/Flk-1. Supporting the notion that PIGF can use only Flt-1 as a receptor, PIGF activated Flt-1 to autophosphorylate, whereas PIGF could not generate signals from KDR/Flk-1. These results indicate that Flt-1, but not KDR/Flk-1, is a receptor for PIGF, suggesting that the weak biological activities of PIGF are due to its use of only part of the available VEGF signaling. These mild characteristics of PIGF may be important for the appropriate development and maintenance of normal placental tissue.
- Subjects :
- 3T3 Cells enzymology
3T3 Cells ultrastructure
Amino Acid Sequence
Animals
Baculoviridae genetics
Base Sequence
Binding, Competitive physiology
Capillary Permeability physiology
DNA, Complementary physiology
Endothelial Growth Factors metabolism
Endothelial Growth Factors pharmacology
Endothelium metabolism
Endothelium ultrastructure
Gene Expression physiology
Guinea Pigs
Heparin
Humans
Lymphokines metabolism
Lymphokines pharmacology
Mice
Molecular Sequence Data
Placenta Growth Factor
Pregnancy Proteins genetics
Pregnancy Proteins pharmacology
Protein-Tyrosine Kinases metabolism
Proto-Oncogene Proteins agonists
Proto-Oncogene Proteins genetics
Receptor Protein-Tyrosine Kinases agonists
Receptor Protein-Tyrosine Kinases genetics
Receptors, Cell Surface metabolism
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
Evans Blue pharmacokinetics
Growth Substances metabolism
Pregnancy Proteins metabolism
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Receptors, Growth Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1044-9523
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 8822205