Department of Immunology Box 3010, Duke University Medical Center, 352 Jones Building, Research Drive, Durham, NC 27710, USA.
Dev Comp Immunol. 2010 Oct;34(10):1109-18. doi: 10.1016/j.dci.2010.06.003. Epub 2010 Jun 19.
In mammals, expression of the three alternatively spliced exons of the tyrosine phosphatase CD45 is regulated by the developmental and activation state of the cell. In comparison, the channel catfish, Ictalurus punctatus, CD45 homolog contains 18 functional alternatively spliced exons. Since very little is known about CD45 regulation in ectothermic vertebrates, this study examines the regulation of catfish CD45 mRNA isoform expression in clonal T and B cells in response to stimulation. Results show that mitogenic stimulation using catfish serum or concanavalin A induced expression of mRNAs for small CD45 isoforms, and isoform message expression was growth curve dependent, i.e. cells in logarithmic phase express message for smaller CD45 isoforms, whereas stationary phase cells express message for longer CD45 isoforms. In addition, cells treated with the protein synthesis inhibitor cycloheximide expressed message for longer CD45 isoforms, and treatment with lactacystin, which blocks protein degradation, rescued smaller isoform message expression. Collectively these data suggested that expression of CD45 isoforms, in catfish, at least at the mRNA level, is "constitutively dynamic" and highly dependent on extracellular stimuli.
在哺乳动物中,酪氨酸磷酸酶 CD45 的三个可变剪接外显子的表达受细胞的发育和激活状态调节。相比之下,鲶鱼(Ictalurus punctatus)的 CD45 同源物包含 18 个具有功能的可变剪接外显子。由于对变温脊椎动物中 CD45 的调节知之甚少,本研究检查了鲶鱼 CD45 mRNA 异构体表达在克隆 T 和 B 细胞中对刺激的反应。结果表明,使用鲶鱼血清或刀豆蛋白 A 进行有丝分裂刺激诱导了小 CD45 异构体的 mRNA 表达,并且异构体的表达与生长曲线有关,即对数期细胞表达较小的 CD45 异构体的 mRNA,而静止期细胞表达较长的 CD45 异构体的 mRNA。此外,用蛋白合成抑制剂环己酰亚胺处理的细胞表达较长的 CD45 异构体的 mRNA,用阻止蛋白降解的乳胞素处理可挽救较小异构体的 mRNA 表达。综上所述,这些数据表明,在鲶鱼中,至少在 mRNA 水平上,CD45 异构体的表达是“组成型动态”的,并且高度依赖于细胞外刺激。