Stehlik Christian, Kroismayr Renate, Dorfleutner Andrea, Binder Bernd R, Lipp Joachim
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, and BMT - Biomolecular Therapeutics GmbH, Brunnerstrasse 59, A-1235 Vienna, Austria.
FEBS Lett. 2004 Jul 2;569(1-3):149-55. doi: 10.1016/j.febslet.2004.05.038.
Using a signal sequence trap for selection of differentially expressed secretory and membrane proteins, we identified a novel member of the adhesion family of G-protein coupled receptors (GPCRs), termed vascular inducible GPCR (VIGR). VIGR contains C1r-C1s, Uegf and Bmp1 (CUB) and pentraxin (PTX)-like modules and a mucin-like spacer, followed by seven transmembrane domains. By surface biotinylation as well as by immunofluorescence analysis we demonstrate that endogenous, highly glycosylated VIGR is expressed on the cell surface of endothelial cells (ECs) upon LPS or thrombin treatment, and inducible expression is mediated by MAP kinases, but not NF-kappaB. We show that VIGR is selectively expressed in ECs derived from larger vessels, but not from microvessels. In summary, VIGR represents a novel GPCR of the adhesion family, which is unique in its long extra-cellular domain comprising CUB and PTX-like modules and in its inducibility by LPS and thrombin in a subset of ECs, suggesting an important function in cell-adhesion and potentially links inflammation and coagulation.
利用信号序列捕获技术筛选差异表达的分泌蛋白和膜蛋白，我们鉴定出一种G蛋白偶联受体（GPCR）粘附家族的新成员，称为血管诱导型GPCR（VIGR）。VIGR包含C1r-C1s、Uegf和Bmp1（CUB）以及五聚体（PTX）样结构域和一个粘蛋白样间隔区，随后是七个跨膜结构域。通过表面生物素化以及免疫荧光分析，我们证明内源性、高度糖基化的VIGR在LPS或凝血酶处理后在内皮细胞（ECs）的细胞表面表达，且诱导表达由丝裂原活化蛋白激酶介导，而非核因子κB。我们发现VIGR在源自较大血管而非微血管的ECs中选择性表达。总之，VIGR代表一种新的粘附家族GPCR，其独特之处在于其长细胞外结构域包含CUB和PTX样结构域，以及在一部分ECs中对LPS和凝血酶的可诱导性，提示其在细胞粘附中具有重要功能，并可能将炎症与凝血联系起来。
