Kendall R L, Thomas K A
Department of Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705-9. doi: 10.1073/pnas.90.22.10705.
Vascular endothelial cell growth factor, a mitogen selective for vascular endothelial cells in vitro that promotes angiogenesis in vivo, functions through distinct membrane-spanning tyrosine kinase receptors. The cDNA encoding a soluble truncated form of one such receptor, fms-like tyrosine kinase receptor, has been cloned from a human vascular endothelial cell library. The mRNA coding region distinctive to this cDNA has been confirmed to be present in vascular endothelial cells. Soluble fms-like tyrosine kinase receptor mRNA, generated by alternative splicing of the same pre-mRNA used to produce the full-length membrane-spanning receptor, encodes the six N-terminal immunoglobulin-like extracellular ligand-binding domains but does not encode the last such domain, transmembrane-spanning region, and intracellular tyrosine kinase domains. The recombinant soluble human receptor binds vascular endothelial cell growth factor with high affinity and inhibits its mitogenic activity for vascular endothelial cells; thus this soluble receptor could act as an efficient specific antagonist of vascular endothelial cell growth factor in vivo.
血管内皮细胞生长因子是一种在体外对血管内皮细胞具有选择性的促分裂原，可在体内促进血管生成，它通过独特的跨膜酪氨酸激酶受体发挥作用。编码一种此类受体（fms样酪氨酸激酶受体）可溶性截短形式的cDNA已从人血管内皮细胞文库中克隆出来。已证实该cDNA特有的mRNA编码区存在于血管内皮细胞中。可溶性fms样酪氨酸激酶受体mRNA由用于产生全长跨膜受体的同一前体mRNA经可变剪接产生，编码N端的六个免疫球蛋白样细胞外配体结合结构域，但不编码最后一个此类结构域、跨膜区和细胞内酪氨酸激酶结构域。重组可溶性人受体以高亲和力结合血管内皮细胞生长因子，并抑制其对血管内皮细胞的促有丝分裂活性；因此，这种可溶性受体在体内可作为血管内皮细胞生长因子的有效特异性拮抗剂。
