XLαs, the extra-long form of the α-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex
XLαs, the extra-long form of the α-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex
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DOI：
10.1073/pnas.0308758101
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发表时间：
2004-06-01
影响因子：
11.1
通讯作者：
Birnbaumer, L
中科院分区：
文献类型：
--
作者：
Abramowitz, J;Grenet, D;Birnbaumer, L
由于交替外显子1的使用，哺乳动物表达两种不同形式的Galpha亚基：存在于所有组织中的典型394-aa Galpha和以更受限的方式表达的700+-aa超长α（XLalpha）。这两个亚基都将受体信号转化为腺苷酸环化酶的刺激。XL外显子编码XLalphas的XL结构域，并且在平行的ORF中编码称为Alex的蛋白质。Alex与XLas的XL结构域相互作用并抑制其腺苷酸环化酶刺激功能。在小鼠、大鼠和人类中，XL外显子被认为贡献422.3、367.3和551.3个密码子，并分别编码390、357和561个氨基酸的Alex蛋白。我们在这里报告说，XL外显子比推测的要长，并且在小鼠、大鼠和人类中分别为XLas贡献了额外的364、430和139个密码子。我们称N-末端延伸的XLalphas为超长Gsalpha或XXLalphas。亚历克斯也更长。它的ORF也在5'方向保持开放约2，000 nt，产生了Alex-extended或AlexX。小鼠脑总RNA的RT-PCR显示整个XXL结构域编码在单个外显子中。此外，我们发现了XXLalphas的两种截短形式，XXLb 1和XXLb 2，其中，由于选择性剪接，Gsa结构域被不同的序列取代。XXLb蛋白可能与AlexX形成稳定的二聚体。N-末端较长的蛋白质可能起调节作用。
Because of the use of alternate exons 1, mammals express two distinct forms of Gsalpha-subunits: the canonical 394-aa Gsalpha present in all tissues and a 700+-aa extra-long alphas (XLalphas) expressed in a more restricted manner. Both subunits transduce receptor signals into stimulation of adenylyl cyclase. The XL exon encodes the XL domain of XLalphas and, in a parallel ORF, a protein called Alex. Alex interacts with the XL domain of XLas and inhibits its adenylyl cyclase-stimulating function. In mice, rats, and humans, the XL exon is thought to contribute 422.3, 367.3, and 551.3 codons and to encode Alex proteins of 390, 357, and 561 aa, respectively. We report here that the XL exon is longer than presumed and contributes in mice, rats, and humans, respectively, an additional 364, 430, and 139 codons to XLas. We called the N-terminally extended XLalphas extra-extra-long Gsalpha, or XXLalphas. Alex is likewise longer. Its ORF also remains open in the 5' direction for approximate to 2,000 nt, giving rise to Alex-extended, or AlexX. RT-PCR of murine total brain RNA shows that the entire XXL domain is encoded in a single exon. Furthermore, we discovered two truncated forms of XXLalphas, XXLb1 and XXLb2, in which, because of alternative splicing, the Gsa domain is replaced by different sequences. XXLb proteins are likely to be found as stable dimers with AlexX. The N-terminally longer proteins may play regulatory roles.