Xu Zheng, Weiss Arthur
Department of Medicine and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0795, USA.
Nat Immunol. 2002 Aug;3(8):764-71. doi: 10.1038/ni822. Epub 2002 Jul 22.
The regulation of receptor-like protein tyrosine phosphatases (RPTPs) is not well understood. Although CD45 can be negatively regulated by dimerization, how dimerization is modulated is unclear. Here we show that various isoforms of CD45 differentially homodimerize in T cells. The dimerization is modulated by the sialylation and O-glycosylation of alternatively spliced CD45 exons in the extracellular domain. Thus, the smallest isoform, CD45RO--which undergoes the least extracellular sialylation and O-glycosylation--homodimerizes with the highest efficiency, resulting in decreased signaling via the T cell receptor. Because CD45 is required for T cell activation, our findings may reveal a mechanism that contributes to the termination of the primary T cell response. Our results not only demonstrate the biological significance of alternative splicing in the immune system, but also suggest a model for regulating RPTP dimerization and function.
类受体蛋白酪氨酸磷酸酶（RPTPs）的调控机制尚未完全明确。尽管CD45可通过二聚化进行负调控，但二聚化是如何被调节的仍不清楚。在此，我们表明CD45的各种同工型在T细胞中以不同方式进行同源二聚化。这种二聚化受细胞外结构域中可变剪接的CD45外显子的唾液酸化和O-糖基化调节。因此，最小的同工型CD45RO——其经历的细胞外唾液酸化和O-糖基化最少——以最高效率进行同源二聚化，导致通过T细胞受体的信号传导减少。由于CD45是T细胞活化所必需的，我们的发现可能揭示了一种有助于终止初始T细胞反应的机制。我们的结果不仅证明了可变剪接在免疫系统中的生物学意义，还提出了一种调节RPTP二聚化和功能的模型。
