DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites
DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites
复制标题
DOI：
10.1111/j.1356-9597.2004.00743.x
复制
发表时间：
2004-06-01
期刊：
影响因子：
2.1
通讯作者：
Akiyama, T
中科院分区：
文献类型：
--
作者：
Moriguchi, T;Haraguchi, K;Akiyama, T
我们已经确定并表征了G蛋白偶联受体（GPCR）家族的新成员，称为DREG。DREG属于LNB-TM7亚家族，具有一个长氨基末端，包含一个CUB结构域、一个PTX结构域、一个激素结合结构域和一个GPCR蛋白水解位点（GPS）结构域。RT-PCR实验和小鼠全载原位杂交表明，DREG在胚胎发育时期的心脏和体体以及成年后的肺中均有高水平表达。当DREG在哺乳动物培养的细胞中短暂表达时，在保守的GPS结构域通过内源性蛋白水解加工产生了一个35-kD片段。这个短片段被发现与细胞膜有关，是典型的gpcr。DPEG在胞外结构域的中间进一步裂解，产生一个含有CUB和PTX结构域的可溶性70-kD片段。这一过程被一种内源性蛋白酶furin抑制剂所抑制，而不受基质金属蛋白酶的抑制。这些结果提高了DREG在发育中发挥作用的可能性，不仅作为受体或粘附分子，而且作为分泌配体。
We have identified and characterized a novel member of the G protein-coupled receptor (GPCR) family, termed DREG. DREG belongs to the LNB-TM7 subfamily and possesses a long amino-terminus that contains a CUB domain, a PTX domain, a hormone binding domain and a GPCR proteolytic site (GPS) domain. RT-PCR experiments and whole mount in situ hybridization in mice showed that DREG is expressed at high levels in the heart and somite during embryogenesis and in the adult lung. When DREG was transiently expressed in mammalian cultured cells, a 35-kD fragment was generated by endogenous proteolytic processing at the conserved GPS domain. This short fragment was found associated with the cell membrane, typical of GPCRs. DPEG was further cleaved in the middle of the extracellular domain, generating a soluble 70-kD fragment containing the CUB and PTX domains. This processing was inhibited by an inhibitor of the endoprotease furin but not of matrix metalloproteinases. These results raise the possibility that DREG plays a role in development, not only as a receptor or an adhesion molecule but also as a secreted ligand.