Itzhaky D, Raz N, Hollander N
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Israel.
J Immunol. 1998 May 1;160(9):4361-6.
The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown. Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI structure serves as a signal-transducing element. However, the division of signaling functions between transmembrane and GPI-anchored proteins is unclear. Studies of distinct membrane-anchored forms of the same protein may resolve this issue. The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane and a GPI-anchored form and hence provides a useful model. We studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating adhesion, CD58 is involved in signal transduction. Incubation of JY cells with immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in secretion of TNF-alpha. We demonstrate that CD58 is associated with protein kinase(s) and with several kinase substrates. We further demonstrate that both CD58 isoforms are involved. CD58 in JY variant cells, which express only the transmembrane form, as well as CD58 in JY variant cells, which express only the GPI-anchored form, are associated with kinase activity. This association results in a phosphorylation pattern that is common to the variant and to wild-type JY cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to interact with kinases is not always dependent on the GPI anchor itself.
糖基磷脂酰肌醇（GPI）锚定的意义尚不清楚。由于GPI锚定蛋白介导信号传导，有人提出GPI结构作为信号转导元件。然而，跨膜蛋白和GPI锚定蛋白之间的信号传导功能划分尚不清楚。对同一蛋白不同膜锚定形式的研究可能会解决这个问题。粘附分子CD58以跨膜和GPI锚定两种形式表达于细胞表面，因此提供了一个有用的模型。我们在人B淋巴母细胞系JY中研究了CD58。除了介导粘附外，CD58还参与信号转导。用固定化抗CD58抗体孵育JY细胞会导致广泛的酪氨酸磷酸化和TNF-α的分泌。我们证明CD58与蛋白激酶及几种激酶底物相关。我们进一步证明两种CD58异构体均参与其中。仅表达跨膜形式的JY变异细胞中的CD58，以及仅表达GPI锚定形式的JY变异细胞中的CD58，均与激酶活性相关。这种关联导致变异细胞和野生型JY细胞出现共同的磷酸化模式。因此，这些发现表明GPI锚定蛋白与激酶相互作用的能力并不总是依赖于GPI锚本身。
