Organization and post-transcriptional processing of focal adhesion kinase gene.
Organization and post-transcriptional processing of focal adhesion kinase gene.
复制标题
DOI：
10.1186/1471-2164-7-198
复制
发表时间：
2006-08-04
期刊：
影响因子：
4.4
通讯作者：
Enslen H
中科院分区：
文献类型：
--
作者：
Corsi JM;Rouer E;Girault JA;Enslen H
粘着斑激酶（FAK）是一种非受体酪氨酸激酶，对胚胎发育到癌症进展的过程至关重要。尽管在啮齿类动物和鸡中已经发现了具有特定分子和功能特性的FAK基因亚型，但FAK基因在整个胚胎发育过程中的组织结构及其产生多种亚型的潜力还不清楚。本论文主要研究FAK在啮齿类动物和人类中的发生、基因组结构及其转录后加工过程。在非脊椎动物物种中发现了FAK和相关PYK 2的单一直系同源物。在棘皮动物分支后的后口动物中可能发生了基因复制，导致PYK 2具有独特的进化特性。FAK和PYK 2的氨基酸序列在其功能域中是保守的，但在其连接区中不是，在C.优雅的。小鼠和人FAK基因的比较揭示了在FAK转录物中存在保守和非保守的5 '-非翻译外显子的多种组合，表明其表达的复杂调控。先前在啮齿动物中描述的四个可变剪接编码外显子（13、14、16和31）在脊椎动物中高度保守。已知调节选择性剪接的顺式调节元件存在于FAK的保守选择性外显子或侧翼内含子中。相比之下，其他报告的人类变异外显子仅限于智人，在某些情况下，其他灵长类动物。这些非保守外显子中的几个可能对应于转座因子。在发育过程中，通过RT-PCR检测小鼠和人脑中保守的替代外显子的包含。包含外显子14和16在胚胎生命结束时达到峰值，而包含外显子13稳定增加，直到成年。对各种组织的研究表明，这些外显子也以组织特异性的方式相互独立地包含在内。替代编码外显子13、14、16和31在脊椎动物中是高度保守的，并且它们在mRNA中的包含是紧密但独立地调节的。因此，这些外显子可能对特定组织或发育过程中的FAK功能至关重要。相反，FAK及其亚型表达的病理性紊乱可导致异常的细胞调节。
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human. A single orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene duplication probably occurred in deuterostomes after the echinoderma embranchment, leading to the evolution of PYK2 with distinct properties. The amino acid sequence of FAK and PYK2 is conserved in their functional domains but not in their linker regions, with the absence of autophosphorylation site in C. elegans. Comparison of mouse and human FAK genes revealed the existence of multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK transcripts suggesting a complex regulation of their expression. Four alternatively spliced coding exons (13, 14, 16, and 31), previously described in rodents, are highly conserved in vertebrates. Cis-regulatory elements known to regulate alternative splicing were found in conserved alternative exons of FAK or in the flanking introns. In contrast, other reported human variant exons were restricted to Homo sapiens, and, in some cases, other primates. Several of these non-conserved exons may correspond to transposable elements. The inclusion of conserved alternative exons was examined by RT-PCR in mouse and human brain during development. Inclusion of exons 14 and 16 peaked at the end of embryonic life, whereas inclusion of exon 13 increased steadily until adulthood. Study of various tissues showed that inclusion of these exons also occurred, independently from each other, in a tissue-specific fashion. The alternative coding exons 13, 14, 16, and 31 are highly conserved in vertebrates and their inclusion in mRNA is tightly but independently regulated. These exons may therefore be crucial for FAK function in specific tissues or during development. Conversely pathological disturbance of the expression of FAK and of its isoforms could lead to abnormal cellular regulation.
登录
查看更多内容
DOI：
10.1016/0169-328x(95)00273-u
发表时间：
1996-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Burgaya, F;Girault, JA
通讯作者：
Girault, JA
影响因子：
10.7
作者：
Castresana, J
通讯作者：
Castresana, J
影响因子：
5.7
作者：
Arold, ST;Hoellerer, MK;Noble, MEM
通讯作者：
Noble, MEM
影响因子：
4.8
作者：
Burgaya, F;Toutant, M;Girault, JA
通讯作者：
Girault, JA
影响因子：
1.2
作者：
García, MG;Toney, SJ;Hille, MB
通讯作者：
Hille, MB