Davies John Q, Chang Gin-Wen, Yona Simon, Gordon Siamon, Stacey Martin, Lin Hsi-Hsien
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
J Biol Chem. 2007 Sep 14;282(37):27343-27353. doi: 10.1074/jbc.M704096200. Epub 2007 Jul 9.
The human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM7 receptor predominantly expressed in myeloid cells, we demonstrate that it forms dimers in a reaction mediated exclusively by the TM7 moiety. We have also identified a naturally occurring but structurally unstable EMR2 splice variant that acts as a dominant negative modulator by dimerizing with the wild type receptor and down-regulating its expression. Additionally, heterodimerization between closely related EGF-TM7 members is shown to result in the modulation of expression and ligand binding properties of the receptors. These findings suggest that receptor homo- and hetero-oligomerization play a regulatory role in modulating the expression and function of leukocyte adhesion-GPCRs.
人类白细胞黏附G蛋白偶联受体（GPCRs），即表皮生长因子（EGF）-TM7蛋白，在本文中被证明可作为同型和异型寡聚体发挥作用。通过对主要在髓样细胞中表达的EGF-TM7受体EMR2进行细胞表面交联、免疫共沉淀和荧光共振能量转移分析，我们证明它在仅由TM7部分介导的反应中形成二聚体。我们还鉴定出一种天然存在但结构不稳定的EMR2剪接变体，它通过与野生型受体二聚化并下调其表达，作为一种显性负调节剂发挥作用。此外，密切相关的EGF-TM7成员之间的异源二聚化被证明会导致受体表达和配体结合特性的调节。这些发现表明，受体同型和异型寡聚化在调节白细胞黏附GPCRs的表达和功能中发挥调节作用。
