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首页> 外文期刊>Genomics >Alternative splicing produces transcripts encoding four variants of mouse G-protein-coupled receptor kinase 6.
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Alternative splicing produces transcripts encoding four variants of mouse G-protein-coupled receptor kinase 6.

机译：选择性剪接产生的转录本编码小鼠G蛋白偶联受体激酶6的四个变体。

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摘要

A family of protein kinases, termed G-protein-coupled receptor kinases (GRK1-6), is known to phosphorylate agonist-occupied G-protein-coupled receptors. We have identified mRNAs encoding four distinct mouse GRK6 isoforms (mGRK6), designated mGRK6-A through mGRK6-D. Mouse GRK6-B and mGRK6-C diverge from the known human GRK6 (577 residues) at residue 560 and are 13 residues longer and 16 residues shorter, respectively, than human GRK6, while mGRK6-A very likely represents the mouse equivalent of human GRK6. Mouse GRK6-D is identical to the other mGRK6 variants in the amino-terminal region, but comprises only 59 of the 263 amino acids of the putative catalytical domain. As mGRK6-D retains the region involved in interacting with activated receptors, but most likely lacks catalytic activity, this variant might represent a naturally occurring inhibitor of other GRKs. Analysis of the genomic organization of mGRK6 gene revealed that the four mRNAs are generated by alternative RNA splicing from a single approximately 14. 5-kb gene, made up of at least 17 exons and located on mouse chromosome 13. Similar to human GRK6, mGRK6-A contains three cysteine residues within its carboxyl-terminal region known to serve as substrates for palmitoylation. Mouse GRK6-B lacks these palmitoylation sites, but carries a basic carboxyl-terminus containing consensus sequences for phosphorylation by protein kinases C and cAMP/cGMP-dependent protein kinases. Mouse GRK6-C displays none of these motifs. Thus, mGRK6-A, mGRK6-B, and mGRK6-C are predicted to differ in terms of their regulation by carboxyl-terminal posttranslational modification. Analysis of mRNA expression revealed that the four mGRK6 mRNAs are differentially expressed in mouse tissues, suggesting that the four mGRK6 isoforms are involved in regulating tissue- or cell type-specific functions in vivo. Copyright 1999 Academic Press.
机译：已知称为G蛋白偶联受体激酶（GRK1-6）的蛋白激酶家族可将激动剂占据的G蛋白偶联受体磷酸化。我们已经确定了编码四个不同的小鼠GRK6亚型（mGRK6），称为mGRK6-A通过mGRK6-D的mRNA。小鼠GRK6-B和mGRK6-C与已知的人GRK6（577个残基）不同，分别比人GRK6长13个残基和短16个残基，而mGRK6-A很可能代表人GRK6的小鼠等效物。小鼠GRK6-D在氨基末端区域与其他mGRK6变体相同，但仅包含推定催化结构域的263个氨基酸中的59个。由于mGRK6-D保留了与活化受体相互作用的区域，但很可能缺乏催化活性，因此该变体可能代表其他GRK的天然抑制剂。 mGRK6基因的基因组组织分析表明，这四个mRNA是由一个大约14个5kb基因组成的，由交替的RNA剪接产生，该基因由至少17个外显子组成，位于小鼠13号染色体上。 -A在其羧基末端区域内包含三个半胱氨酸残基，已知其充当棕榈酰化的底物。小鼠GRK6-B缺少这些棕榈酰化位点，但带有一个基本的羧基末端，该末端含有一个共有序列，用于通过蛋白激酶C和cAMP / cGMP依赖性蛋白激酶进行磷酸化。鼠标GRK6-C没有显示这些主题。因此，据预测，mGRK6-A，mGRK6-B和mGRK6-C在通过羧基末端翻译后修饰进行调节方面会有所不同。对mRNA表达的分析表明，四种mGRK6 mRNA在小鼠组织中差异表达，表明这四种mGRK6同工型参与体内调节组织或细胞类型特异性功能。版权所有1999 Academic Press。

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