Rovedo Mark, Longnecker Richard
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Ward 6-231, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
J Virol. 2007 Jan;81(1):84-94. doi: 10.1128/JVI.01302-06. Epub 2006 Oct 11.
Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and in vivo. LMP2A has important roles in modulating B-cell receptor (BCR) signal transduction by associating with the cellular tyrosine kinases Lyn and Syk via specific phosphotyrosine motifs found within the LMP2A N-terminal tail domain. LMP2A has been shown to alter normal BCR signal transduction in B cells by reducing levels of Lyn and by blocking tyrosine phosphorylation and calcium mobilization following BCR cross-linking. Although little is currently known about the function of LMP2B in B cells, the similarity in structure between LMP2A and LMP2B suggests that they may localize to the same cellular compartments. To investigate the function of LMP2B, B-cell lines expressing LMP2A, LMP2B, LMP2A/LMP2B, and the relevant vector controls were analyzed. As was previously shown, cells expressing LMP2A had a dramatic block in normal BCR signal transduction as measured by calcium mobilization and tyrosine phosphorylation. There was no effect on BCR signal transduction in cells expressing LMP2B. Interestingly, when LMP2B was expressed in conjunction with LMP2A, there was a restoration of normal BCR signal transduction upon BCR cross-linking. The expression of LMP2B did not alter the cellular localization of LMP2A but did bind to and prevent the phosphorylation of LMP2A. A restoration of Lyn levels, but not a change in LMP2A levels, was also observed in cells coexpressing LMP2B with LMP2A. From these results, we conclude that LMP2B modulates LMP2A activity.
潜伏膜蛋白2A（LMP2A）和LMP2B是爱泼斯坦-巴尔病毒（EBV）在细胞培养和体内感染的B细胞中潜伏期间表达的病毒蛋白。LMP2A通过其N末端尾巴结构域内的特定磷酸酪氨酸基序与细胞酪氨酸激酶Lyn和Syk结合，在调节B细胞受体（BCR）信号转导中发挥重要作用。研究表明，LMP2A通过降低Lyn水平以及在BCR交联后阻断酪氨酸磷酸化和钙动员，改变B细胞中正常的BCR信号转导。尽管目前对LMP2B在B细胞中的功能了解甚少，但LMP2A和LMP2B在结构上的相似性表明它们可能定位于相同的细胞区室。为了研究LMP2B的功能，对表达LMP2A、LMP2B、LMP2A/LMP2B的B细胞系以及相关载体对照进行了分析。如先前所示，通过钙动员和酪氨酸磷酸化测量，表达LMP2A的细胞在正常BCR信号转导中存在显著阻滞。表达LMP2B的细胞中BCR信号转导没有受到影响。有趣的是，当LMP2B与LMP2A共同表达时，BCR交联后正常的BCR信号转导得以恢复。LMP2B的表达没有改变LMP2A的细胞定位，但确实与LMP2A结合并阻止其磷酸化。在LMP2B与LMP2A共表达的细胞中还观察到Lyn水平的恢复，但LMP2A水平没有变化。从这些结果中，我们得出结论，LMP2B调节LMP2A的活性。
