BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation
BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation
复制标题
DOI：
10.1128/mcb.23.16.5664-5679.2003
复制
发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Patterson, C
中科院分区：
文献类型：
--
作者：
Moser, M;Binder, O;Patterson, C
内皮细胞前体细胞的发育对于血管生成至关重要。我们筛选了发育中的小鼠胚状体的内皮细胞前体中差异表达的转录本。我们克隆了编码蛋白质的完整 cDNA，该蛋白质包含氨基末端信号肽、五个富含半胱氨酸的结构域、冯维勒布兰德 D 结构域和胰蛋白酶抑制剂结构域。我们将这种蛋白命名为 BMPER（骨形态发生蛋白 [BMP] 结合内皮细胞前体衍生调节因子）。 BMPER 在 flk-1 阳性细胞中特异性表达，并且与这些细胞中 flk-1 诱导的时间过程平行。小鼠胚胎的原位杂交显示了背侧中线染色和主动脉-性腺-中肾区域的染色，已知该区域是血管前体细胞的宿主。 BMPER 是一种分泌蛋白，可直接与 BMP2、BMP4 和 BMP6 相互作用并拮抗 BMP4 依赖性 Smad5 激活。在非洲爪蟾胚胎中，腹侧注射 BMPER mRNA 会导致轴复制和 Xvent-1（Smad 信号下游靶标）表达下调。在胚状体分化测定中，胚状体中内皮细胞的BMP4依赖性分化也被BMPER拮抗。综上所述，我们的数据表明 BMPER 是一种新型 BMP 结合蛋白，由内皮细胞前体细胞表达，具有 BMP 拮抗活性，并可能通过调节局部 BNIP 活性在内皮细胞分化中发挥作用。
The development of endothelial cell precursors is essential for vasculogenesis. We screened for differentially expressed transcripts in endothelial cell precursors in developing mouse embryoid bodies. We cloned a complete cDNA encoding a protein that contains an amino-terminal signal peptide, five cysteine-rich domains, a von Willebrand D domain, and a trypsin inhibitor domain. We termed this protein BMPER (bone morphogenetic protein [BMP] -binding endothelial cell precursor-derived regulator). BMPER is specifically expressed in flk-1-positive cells and parallels the time course of flk-1 induction in these cells. In situ hybridization in mouse embryos demonstrates dorsal midline staining and staining of the aorto-gonadal-mesonephric region, which is known to host vascular precursor cells. BMPER is a secreted protein that directly interacts with BMP2, BMP4, and BMP6 and antagonizes BMP4-dependent Smad5 activation. In Xenopus embryos, ventral injection of BMPER mRNA results in axis duplication and downregulation of the expression of Xvent-1 (downstream target of Smad signaling). In an embryoid body differentiation assay, BMP4-dependent differentiation of endothelial cells in embryoid bodies is also antagonized by BMPER. Taken together, our data indicate that BMPER is a novel BMP-binding protein that is expressed by endothelial cell precursors, has BMP-antagonizing activity, and may play a role in endothelial cell differentiation by modulating local BNIP activity.