Ariel Ortal, Kukulansky Tova, Raz Nava, Hollander Nurit
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Cell Signal. 2004 Jun;16(6):667-73. doi: 10.1016/j.cellsig.2003.08.015.
The adhesion molecule CD58 is involved in intercellular adhesion and in signal transduction. It is natively expressed in both a transmembrane form and a glycosylphosphatidylinositol (GPI)-anchored form, and hence provides a model for the study of two distinct membrane-anchored forms of the same protein in the same cell. We demonstrate here that the two isoforms of CD58 are localized in distinct membrane compartments. The GPI-anchored form localizes in lipid rafts, while the transmembrane form resides in nonraft domains. In addition to distinct membrane localization, the two isoforms of CD58 differ in their association with protein kinases. GPI-anchored CD58, residing in raft domains, is constitutively associated with protein kinases. However, cross-linking mediates a substantial increase in kinase activity which is predominantly associated with the transmembrane CD58 in nonraft membrane domains. The extensive inducible kinase activity, associated with transmembrane CD58, is demonstrated in wild-type cells as well as in GPI-deficient variant cells. Thus, although the transmembrane CD58 is excluded from rafts, it may trigger signaling independently of the GPI-linked isoform.
黏附分子CD58参与细胞间黏附和信号转导。它天然以跨膜形式和糖基磷脂酰肌醇（GPI）锚定形式表达，因此为研究同一细胞中同一蛋白质的两种不同膜锚定形式提供了一个模型。我们在此证明，CD58的两种异构体定位于不同的膜区室。GPI锚定形式定位于脂筏，而跨膜形式位于非脂筏结构域。除了不同的膜定位外，CD58的两种异构体在与蛋白激酶的结合方面也有所不同。位于脂筏结构域的GPI锚定CD58与蛋白激酶组成性结合。然而，交联介导激酶活性大幅增加，这主要与非脂筏膜结构域中的跨膜CD58相关。与跨膜CD58相关的广泛的诱导性激酶活性在野生型细胞以及GPI缺陷变体细胞中均得到证实。因此，尽管跨膜CD58被排除在脂筏之外，但它可能独立于GPI连接的异构体触发信号传导。
