描述：
VEGF R1 (vascular endothelial growth factor receptor 1), also called Flt-1 (Fmslike tyrosine
kinase), is a 180 kDa type I transmembrane glycoprotein in the class III subfamily of receptor
tyrosine kinases (RTKs).While family members VEGF R1, VEGF R2/KDR/Flk-1 and VEGF R3/Flt-4
are all mainly expressed on endothelial cells and play central roles in vasculogenesis,
angiogenesis, and lymphangiogenesis, only VEGF R1 is expressed on macrophages, and mainly
plays inhibitory roles. VEGF R1 expression is also reported on osteoblasts, placental
trophoblasts, renal mesangial cells, and some hematopoietic stem cells. Like other class III
RTKs, human VEGF R1 contains a signal peptide (aa 1-22), an extracellular domain (ECD aa
27-758) with seven Iglike repeats, a transmembrane domain (aa 759-780) and a cytoplasmic
region (aa 781-1338) with a tyrosine kinase domain and several autocatalytic phosphotyrosine
sites. Human VEGF R1 ECD shares 78%, 78%, 84%, 87%, and 90% aa sequence identity with
mouse, rat, porcine, canine and equine VEGF R1, respectively. Soluble forms of the VEGF R1
ECD are produced by alternative splicing, and may also be shed during regulated intracellular
proteolysis. Both soluble and transmembrane forms can inhibit angiogenesis by binding
and sequestering its ligands, VEGF (VEGF-A), VEGF-B or PlGF (6-11). VEGF R1 dimerizes upon
ligand binding, which can include heterodimerization with VEGF R2 that modifies VEGF
R2mediated endothelial proliferation and vessel branching. VEGF R1 binds VEGF with higher
affinity than does VEGF R2, but shows weaker kinase activity. Both PlGF and VEGF induce
autophosphorylation of transmembrane VEGF R1. While deletion of mouse VEGF R1 is lethal
due to overgrowth and disorganization of the vasculature, kinase-inactive mutants are viable.
VEGF R1 is up-regulated during hypoxia, and participates in neovascularization and wound
healing. VEGF R1 engagement on monocyte/macrophage lineage cells enhances their
migration, and release of growth factors and cytokines. Lymphangiogenesis, angiogenesis,
and growthpromoting effects of VEGF R1 are thought to result from enhanced migration of
macrophages from the bone marrow to tumors and tissues where they recruit endothelial
progenitors. Circulating levels of VEGF R1 increase during pregnancy and are further elevated
in preeclampsia.
原厂资料：
VEGF R1 (vascular endothelial growth factor receptor 1), also called Flt-1 (Fmslike tyrosine
kinase), is a 180 kDa type I transmembrane glycoprotein in the class III subfamily of receptor
tyrosine kinases (RTKs).While family members VEGF R1, VEGF R2/KDR/Flk-1 and VEGF R3/Flt-4
are all mainly expressed on endothelial cells and play central roles in vasculogenesis,
angiogenesis, and lymphangiogenesis, only VEGF R1 is expressed on macrophages, and mainly
plays inhibitory roles. VEGF R1 expression is also reported on osteoblasts, placental
trophoblasts, renal mesangial cells, and some hematopoietic stem cells. Like other class III
RTKs, human VEGF R1 contains a signal peptide (aa 1-22), an extracellular domain (ECD aa
27-758) with seven Iglike repeats, a transmembrane domain (aa 759-780) and a cytoplasmic
region (aa 781-1338) with a tyrosine kinase domain and several autocatalytic phosphotyrosine
sites. Human VEGF R1 ECD shares 78%, 78%, 84%, 87%, and 90% aa sequence identity with
mouse, rat, porcine, canine and equine VEGF R1, respectively. Soluble forms of the VEGF R1
ECD are produced by alternative splicing, and may also be shed during regulated intracellular
proteolysis. Both soluble and transmembrane forms can inhibit angiogenesis by binding
and sequestering its ligands, VEGF (VEGF-A), VEGF-B or PlGF (6-11). VEGF R1 dimerizes upon
ligand binding, which can include heterodimerization with VEGF R2 that modifies VEGF
R2mediated endothelial proliferation and vessel branching. VEGF R1 binds VEGF with higher
affinity than does VEGF R2, but shows weaker kinase activity. Both PlGF and VEGF induce
autophosphorylation of transmembrane VEGF R1. While deletion of mouse VEGF R1 is lethal
due to overgrowth and disorganization of the vasculature, kinase-inactive mutants are viable.
VEGF R1 is up-regulated during hypoxia, and participates in neovascularization and wound
healing. VEGF R1 engagement on monocyte/macrophage lineage cells enhances their
migration, and release of growth factors and cytokines. Lymphangiogenesis, angiogenesis,
and growthpromoting effects of VEGF R1 are thought to result from enhanced migration of
macrophages from the bone marrow to tumors and tissues where they recruit endothelial
progenitors. Circulating levels of VEGF R1 increase during pregnancy and are further elevated
in preeclampsia.
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