Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors
Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors
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DOI：
10.4049/jimmunol.164.10.5287
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发表时间：
2000-05-15
影响因子：
4.4
通讯作者：
Screaton, GR
中科院分区：
文献类型：
--
作者：
ten Dam, GB;Zilch, CF;Screaton, GR
CD45是一种具有酪氨酸磷酸酶活性的跨膜糖蛋白，参与细胞信号传导。CD45在大多数白细胞的表面上表达，并且可以通过包含或跳过三个可变外显子（4、5和6或A、B和C）来选择性剪接以产生多达八种同种型。主要表达外显子A的CD45亚型（CD45RA），而活化细胞失去外显子A的表达，形成低m.w. CD45亚型，包括CD45RO。关于控制激活时发生的CD45剪接转换的特定因素知之甚少。在这项研究中，我们研究了SR家族的剪接因子，其中，像CD45，表达在组织特异性模式，并已被证明可以调节各种转录的选择性剪接的影响。我们发现，特定的SR蛋白对CD45剪接有拮抗作用，导致外显子包含或跳跃。此外，我们能够证明在T细胞活化过程中SR蛋白表达模式的特定变化。
CD45 is a transmembrane glycoprotein possessing tyrosine phosphatase activity, which is involved in cell signaling. CD45 is expressed on the surface of most leukocytes and can be alternatively spliced by the inclusion or skipping of three variable exons (4, 5, and 6 or A, B, and C) to produce up to eight isoforms, In T cells, the splicing pattern of CD45 isoforms changes after activation; naive cells express high m.w. isoforms of CD45 which predominantly express exon A (CD45RA), whereas activated cells lose expression of exon A to form low m.w. isoforms of CD45 including CD45RO. Little is known about the specific factors controlling the switch in CD45 splicing which occurs on activation. In this study, we examined the influence of the SR family of splicing factors, which, like CD45, are expressed in tissue-specific patterns and have been shown to modulate the alternative splicing of a variety of transcripts. We show that specific SR proteins have antagonistic effects on CD45 splicing, leading either to exon inclusion or skipping. Furthermore, we were able to demonstrate specific changes in the SR protein expression pattern during T cell activation.