Katzman Rebecca B, Longnecker Richard
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Virol. 2004 Oct;78(20):10878-87. doi: 10.1128/JVI.78.20.10878-10887.2004.
Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed constitutively in lipid rafts in latently infected B lymphocytes. Lipid rafts are membrane microdomains enriched in cholesterol and sphingolipids selective for specific protein association. Lipid rafts have been shown to be necessary for B-cell receptor (BCR) signal transduction. LMP2A prevents BCR recruitment to lipid rafts, thereby abrogating BCR function. As LMP2A is palmitoylated, whether this fatty acid modification is necessary for LMP2A to localize to lipid rafts and for protein function was investigated. LMP2A palmitoylation was confirmed in latently infected B cells. LMP2A was found to be palmitoylated on multiple cysteines only by S acylation. An LMP2A mutant that was not palmitoylated was identified and functioned similar to wild-type LMP2A; unmodified LMP2A localized to lipid rafts, was tyrosine phosphorylated, was associated with LMP2A-associated proteins, was ubiquitinated, and was able to block calcium mobilization following BCR cross-linking. Therefore, palmitoylation of LMP2A is not required for LMP2A targeting to buoyant complexes or for function.
爱泼斯坦-巴尔病毒(EBV)潜伏膜蛋白2A(LMP2A)在潜伏感染的B淋巴细胞的脂筏中持续表达。脂筏是富含胆固醇和鞘脂的膜微区,对特定蛋白质结合具有选择性。脂筏已被证明是B细胞受体(BCR)信号转导所必需的。LMP2A可阻止BCR募集到脂筏,从而消除BCR功能。由于LMP2A被棕榈酰化,因此研究了这种脂肪酸修饰对于LMP2A定位于脂筏和蛋白质功能是否必要。在潜伏感染的B细胞中证实了LMP2A的棕榈酰化。发现LMP2A仅通过S酰化在多个半胱氨酸上被棕榈酰化。鉴定出未被棕榈酰化的LMP2A突变体,其功能与野生型LMP2A相似;未修饰的LMP2A定位于脂筏,被酪氨酸磷酸化,与LMP2A相关蛋白相关,被泛素化,并且能够在BCR交联后阻断钙动员。因此,LMP2A靶向漂浮复合物或发挥功能不需要LMP2A的棕榈酰化。