Gires O, Zimber-Strobl U, Gonnella R, Ueffing M, Marschall G, Zeidler R, Pich D, Hammerschmidt W
GSF-Research Center for Environment and Health, Institut für Klinische Molekularbiologie und Tumorgenetik, Marchioninistrasse 25, D-81377 Munich, Germany.
EMBO J. 1997 Oct 15;16(20):6131-40. doi: 10.1093/emboj/16.20.6131.
Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is an integral membrane protein which has transforming potential and is necessary but not sufficient for B-cell immortalization by EBV. LMP1 molecules aggregate in the plasma membrane and recruit tumour necrosis factor receptor (TNF-R) -associated factors (TRAFs) which are presumably involved in the signalling cascade leading to NF-kappaB activation by LMP1. Comparable activities are mediated by CD40 and other members of the TNF-R family, which implies that LMP1 could function as a receptor. LMP1 lacks extended extracellular domains similar to beta-adrenergic receptors but, in contrast, it also lacks any motifs involved in ligand binding. By using LMP1 mutants which can be oligomerized at will, we show that the function of LMP1 in 293 cells and B cells is solely dependent on oligomerization of its carboxy-terminus. Biochemically, oligomerization is an intrinsic property of the transmembrane domain of wild-type LMP1 and causes a constitutive phenotype which can be conferred to the signalling domains of CD40 or the TNF-2 receptor. In EBV, immortalized B cells cross-linking in conjunction with membrane targeting of the carboxy-terminal signalling domain of LMP1 is sufficient for its biological activities. Thus, LMP1 acts like a constitutively activated receptor whose biological activities are ligand-independent.
爱泼斯坦-巴尔病毒（EBV）的潜伏膜蛋白1（LMP1）是一种整合膜蛋白，具有转化潜能，是EBV使B细胞永生化所必需但不充分的条件。LMP1分子聚集在质膜中，并募集肿瘤坏死因子受体（TNF-R）相关因子（TRAFs），这些因子可能参与导致LMP1激活核因子-κB的信号级联反应。CD40和TNF-R家族的其他成员介导类似的活性，这意味着LMP1可以作为一种受体发挥作用。LMP1缺乏类似于β-肾上腺素能受体的延长细胞外结构域，但与之相反的是，它也缺乏任何参与配体结合的基序。通过使用可随意寡聚化的LMP1突变体，我们表明LMP1在293细胞和B细胞中的功能仅取决于其羧基末端的寡聚化。从生化角度来看，寡聚化是野生型LMP1跨膜结构域的固有特性，并导致一种组成型表型，这种表型可以赋予CD40或TNF-2受体的信号结构域。在EBV中，永生化B细胞的交联以及LMP1羧基末端信号结构域的膜靶向对于其生物学活性而言就足够了。因此，LMP1的作用类似于一种组成型激活的受体，其生物学活性不依赖于配体。
