Genomic organization and differential expression of Kalirin isoforms

Genomic organization and differential expression of Kalirin isoforms
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DOI:
10.1016/s0378-1119(02)00386-4
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发表时间:
2002-02-06
期刊:
影响因子:
3.5
通讯作者:
Mains, RE
Mains, RE
中科院分区:
生物学3区
文献类型:
--
作者:
McPherson, CE;Eipper, BA;Mains, RE

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多结构域鸟嘌呤核苷酸(GDP/GTP)交换因子(GEF)蛋白协调不同的输入信号的肌动蛋白细胞骨架。哺乳动物有两种这样的蛋白质(Kalirin,Trio),而果蝇有一种,它在神经系统内外发挥着重要作用。对于Kalirin,通过选择性剪接和使用选择性转录起始位点产生含有功能结构域的不同组合的许多同种型。这些不同的同种型潜在地允许多种蛋白质与Kalirin相互作用,从而影响功能结构域的活性。人类和大鼠一样,表达大量Kalirin同种型。mRNA,并且我们鉴定了一种新的Kalirin亚型,仅包含第二个GEF结构域。Kalirin亚型主要在脑中表达,而Trio在更广泛的组织中表达。Kalirin的选择性剪接和转录在大鼠和人类发育期间受到差异调节,导致在不同时间和位置表达含有不同功能结构域的Kalirin同种型。Kalirin在整个生命过程中在皮质中的流行表明在轴突发育和成熟大脑中的作用。(C)出版社:Elsevier Science B. V.
Multidomain guanine nucleotide (GDP/GTP) exchange factor (GEF) proteins coordinate diverse inputs that signal the actin cytoskeleton. Mammals have two such proteins (Kalirin, Trio), while Drosophila has one, which plays essential roles within and outside the nervous system. For Kalirin, numerous isoforms containing different combinations of functional domains are generated through alternative splicing and use of alternative transcriptional start sites. These different isoforms potentially allow a wide variety of proteins to interact with Kalirin, thereby affecting the activity of the functional domains. Humans, like rats, express a large set of Kalirin isoform. mRNAs, and we identified a novel Kalirin isoform, containing only the second GEF domain. Kalirin isoforms are predominantly expressed in the brain, while Trio is expressed in a wider variety of tissues. Alternative splicing and transcription of Kalirin are differentially regulated during development in rats and humans, resulting in expression of isoforms of Kalirin containing different functional domains at different times and locations. The prevalence of Kalirin in the cortex throughout life suggests roles in axonal development and the mature brain. (C) 2002 Published by Elsevier Science B.V.