Alternative splice variants of doublecortin-like kinase are differentially expressed and have different kinase activities
Alternative splice variants of doublecortin-like kinase are differentially expressed and have different kinase activities
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DOI：
10.1074/jbc.m111981200
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发表时间：
2002-05-17
影响因子：
4.8
通讯作者：
Reiner, O
中科院分区：
文献类型：
--
作者：
Burgess, HA;Reiner, O
mRNA转录物的选择性剪接扩大了来自单个基因位点的蛋白质产物的范围。先前已报道了DCLK（双皮质素样激酶）的几种剪接变体。在这里，我们报告的基因组组织的剪接变异体的DCLK和检查的表达谱的两个剪接变异体影响激酶域的DCLK和CPG 16（候选可塑性基因16），一个含有精氨酸丰富的结构域和其他影响的C末端的蛋白质。这些剪接选择在胚胎和成人脑中差异表达。这两种剪接变体破坏DCLK PEST结构域，但是，所有剪接变体仍然敏感的钙蛋白酶的蛋白水解。DCLK的成人特异性C-末端剪接变体具有降低的自磷酸化活性，但相对于胚胎剪接变体，髓鞘碱性蛋白的激酶活性相似。剪接变异体增加了一个富含精氨酸的结构域，在Ser-382处获得了一个自磷酸化位点。虽然这种蛋白质亚型主要在成人大脑中表达，但磷酸化形式在胚胎大脑和成人嗅球中强烈富集，表明可能在迁移神经元中起作用。
Alternative splicing of mRNA transcripts expands the range of protein products from a single gene locus. Several splice variants of DCLK (doublecortin-like kinase) have previously been reported. Here, we report the genomic organization underlying the splice variants of DCLK and examine the expression profile of two splice variants affecting the kinase domain of DCLK and CPG16 (candidate plasticity gene 16), one containing an Arg-rich domain and the other affecting the C terminus of the protein. These splice alternatives were differentially expressed in embryonic and adult brain. Both splice variants disrupted DCLK PEST domains; however, all splice variants remained sensitive to proteolysis by calpain. The adult-specific C-terminal splice variant of DCLK had reduced autophosphorylation activity, but similar kinase activity for myelin basic protein relative to the embryonic splice variant. The splice variant adding an Arg-rich domain gained an autophosphorylation site at Ser-382. Although this protein isoform was expressed mainly in the adult brain, the phosphorylated form was strongly enriched in embryonic brain and adult olfactory bulb, suggesting a possible role in migrating neurons.