Longnecker R, Merchant M, Brown M E, Fruehling S, Bickford J O, Ikeda M, Harty R N
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois, 60611, USA.
Exp Cell Res. 2000 Jun 15;257(2):332-40. doi: 10.1006/excr.2000.4900.
Epstein-Barr virus (EBV) is a human herpesvirus which establishes a lifelong latent infection in B lymphocytes. Latent membrane protein 2A (LMP2A) is expressed in both humans with EBV latent infection and EBV immortalized cell lines grown in culture. Previous studies have shown that the amino terminal domain of LMP2A, which contains eight tyrosines, associates with a variety of cellular proteins via SH2-phosphotyrosine interactions. Also contained within the LMP2A amino terminal domain are five proline-rich regions, three of which possess the PxxP core consensus sequence required for interacting with SH3 domains and two of which possess the PPxY core consensus sequence (PY motif) required for interacting with class I type WW domains. In the current study, the ability of LMP2A to interact with either modular SH3 or WW domains was investigated. The results of these studies indicate that the two LMP2A PY motifs interact strongly with representative class I WW domains, but not with representative class II WW domains. In contrast, no interactions were detected between LMP2A and any of the five different SH3 domains tested. These data demonstrate that a subset of the conserved proline-rich motifs within the amino terminus of LMP2A can potentially mediate interactions with cellular proteins and may play a role in EBV-mediated latency and/or transformation.
爱泼斯坦-巴尔病毒（EBV）是一种人类疱疹病毒，可在B淋巴细胞中建立终身潜伏感染。潜伏膜蛋白2A（LMP2A）在EBV潜伏感染的人类以及培养的EBV永生化细胞系中均有表达。先前的研究表明，LMP2A的氨基末端结构域含有八个酪氨酸，通过SH2-磷酸酪氨酸相互作用与多种细胞蛋白相关联。LMP2A氨基末端结构域中还包含五个富含脯氨酸的区域，其中三个具有与SH3结构域相互作用所需的PxxP核心共有序列，另外两个具有与I类WW结构域相互作用所需的PPxY核心共有序列（PY基序）。在本研究中，研究了LMP2A与模块化SH3或WW结构域相互作用的能力。这些研究结果表明，LMP2A的两个PY基序与代表性的I类WW结构域强烈相互作用，但与代表性的II类WW结构域不相互作用。相比之下，在LMP2A与所测试的五个不同SH3结构域之间未检测到相互作用。这些数据表明，LMP2A氨基末端内保守的富含脯氨酸基序的一个子集可能潜在地介导与细胞蛋白的相互作用，并可能在EBV介导的潜伏和/或转化中发挥作用。
