EPIDERMAL GROWTH-FACTOR RECEPTOR IS DOWN-REGULATED BY A 10,400-MW PROTEIN ENCODED BY THE E3 REGION OF ADENOVIRUS
EPIDERMAL GROWTH-FACTOR RECEPTOR IS DOWN-REGULATED BY A 10,400-MW PROTEIN ENCODED BY THE E3 REGION OF ADENOVIRUS
复制标题
DOI：
10.1016/0092-8674(89)90179-7
复制
发表时间：
1989-04-07
期刊：
影响因子：
64.5
通讯作者：
WOLD, WSM
中科院分区：
文献类型：
--
作者：
CARLIN, CR;TOLLEFSON, AE;WOLD, WSM
表皮生长因子（EGF）与特异性高亲和力受体（EGF-R）结合，诱导溶酶体内体特异性内化和配体-受体复合物降解。我们在这里报告，EGF-R是下调以类似的方式在早期感染的各种细胞类型的C组人腺病毒。这种效应不是病毒进入的功能，也不是由于膜蛋白的非特异性周转增加。使用一系列病毒缺失突变体，负责EGF-R下调的基因被定位到E3转录单位。E3基因产物是一种分子量为10，400（10.4K）的蛋白质，可诱导EGF-R的内化和降解，但不影响EGF-R前体的合成。10.4K蛋白不是EGF样自分泌生长因子，但在序列上与EGF-R中跨膜结构域胞质面的区域相似。这表明腺病毒感染过程中EGF-R的下调可能是通过一种新的机制发生的，该机制涉及由10.4K和EGF-R组成的异源寡聚体的形成。
Epidermal growth factor (EGF) binds to specific high affinity receptors (EGF-Rs) and induces endosome-specific internalization and degradation of ligand-receptor complexes in lysosomes. We report here that EGF-R is down-regulated in an analogous manner during early infection of a variety of cell types by group C human adenoviruses. This effect is not a function of viral entry, nor is it due to a nonspecific increase in turnover of membrane proteins. Using a series of virus deletion mutants, the gene responsible for EGF-R down-regulation was mapped to the E3 transcription unit. The E3 gene product, a protein of MW 10,400 (10.4K), induces internalization and degradation of EGF-R, but does not affect synthesis of the EGF-R precursor. The 10.4K protein is not an EGF-like autocrine growth factor, but is similar in sequence to a region in EGF-R at the cytoplasmic face of the transmembrane domain. This suggests that down-regulation of EGF-R during adenovirus infection may occur by a novel mechanism that involves the formation of hetero-oligomers composed of 10.4K and EGF-R.