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Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta.

机译:通过与雌激素受体β的蛋白质相互作用鉴定人Mnk2基因(MKNK2)。

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We have identified and characterized the human Mnk2 gene (HGMW-approved gene symbol MKNK2) through a yeast two-hybrid screen in which the Mnk2 protein interacted with the ligand-binding domain of estrogen receptor beta (ERbeta). Human Mnk2 is homologous to murine Mnk2 ( approximately 94% identical) and human Mnk1 (71% identical), both of which encode MAP kinase interacting kinases that are phosphorylated and activated by ERK1 and 2. This report presents a thorough genomic sequence analysis revealing that the human Mnk2 gene has two C-terminal splice variants, designated here as Mnk2a and Mnk2b. These two isoforms are identical over the first 385 amino acids of the coding sequence and differ only in the final exon which encodes an additional 80 residues for Mnk2a and 29 residues for Mnk2b. A more detailed biological analysis in yeast showed that the Mnk2 interaction was selective for ERbeta as opposed to ERalpha and that the interaction was specific to Mnk2b as opposed to Mnk2a or Mnk1. This pattern was reproduced in a mammalian two-hybrid system using a completely different set of fusion partners; and in both yeast and mammalian systems, the addition of estradiol decreased the interaction. While it remains unknown whether ERbeta is a substrate of Mnk2, the interaction of these two proteins is reminiscent of ERalpha and ribosomal S6 kinase (p90-RSK), another MAP kinase-regulated kinase homologous to Mnk2 that is known to phosphorylate ERalpha. Copyright 2000 Academic Press.
机译:我们已经通过酵母两杂交筛选鉴定和表征了人类Mnk2基因(HGMW批准的基因符号MKNK2),其中Mnk2蛋白与雌激素受体β(ERbeta)的配体结合域相互作用。人Mnk2与鼠Mnk2(约94%相同)和人Mnk1(71%相同)同源,两者均编码被ERK1和2磷酸化并激活的MAP激酶相互作用激酶。该报告提供了全面的基因组序列分析,揭示了人Mnk2基因具有两个C端剪接变体,在此称为Mnk2a和Mnk2b。这两个同工型在编码序列的前385个氨基酸上是相同的,仅在最终外显子上有所不同,该外显子编码Mnk2a的另外80个残基和Mnk2b的29个残基。酵母中更详细的生物学分析表明,Mnk2相互作用对ERbeta具有选择性,而不是ERalpha,并且该相互作用对Mnk2b具有特异性,而与Mnk2a或Mnk1相反。使用完全不同的一组融合伴侣,在哺乳动物的双杂交系统中复制了这种模式。在酵母和哺乳动物系统中,添加雌二醇都会降低相互作用。尽管还不清楚ERbeta是否是Mnk2的底物,但这两种蛋白的相互作用让人联想到ERalpha和核糖体S6激酶(p90-RSK),这是另一种与Mnk2同源的MAP激酶调节的激酶,已知可磷酸化ERalpha。版权所有2000学术出版社。

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