G蛋白偶联受体激酶(GRKs)对GPCR的同源脱敏起着重要作用。受体被GRKs磷酸化激活后，会促进其与抑制蛋白高亲和性结合，结果阻遏了与G蛋白的结合。直接结合活跃的GPCRs可以激活GRKs，所以GRKs往往选择性的只磷酸化激活形式的受体，而不顾这些受体内基质肽的可接近性或者他们含有丝氨酸苏氨酸序列。
现在知道哺乳动物的GRKs可以分为三个主要的类别，但是早期的GRK进化机制却不明确。最近，美国范德堡大学的Eugenia V. Gurevich等人做了一项关于G蛋白偶联受体激酶的起源以及进化的研究，他们发现，GRKs明显早于动物出现。相关论文发表于3月19日的美国《公共科学图书馆·综合》（PLoS One）上。
Eugenia V. Gurevich指出：GRKs出现在真核生物进化早期，在那个时期，一个类似于核糖体蛋白S6激酶的激酶结构插入到了RGS结构域的一个环状结构里，结果形成了GRKs。GRKs在多细胞动物中形成了两个分支，一个分支包括GRK2和GRK3，另一个包括剩下所有的GRKs。在脊椎动物中，GRKs则主要分为GRK1-GRK7和GRK4-GRK5-GRK6两大类。两种古分支中的一种,被发现早在丝盘虫时期便已存在。几种原生生物，两种卵菌类和单细胞褐藻含有一种GRK样的蛋白，这表明早在多细胞生物起源之前，激酶结构便已插入到RGS结构域。两种GRK家族在N端以及C端获得了不同的结构单元，而这些结构单元主要负责细胞膜的招募和受体的偶联。
因此，研究结果表明，GRKs明显早于动物出现，并快速的在后生动物中扩散，当然，这很可能是由于快速运动的动物需要对信号迅速调节所致。（生物谷Deepblue编译）
doi: 10.1371/journal.pone.0033806
PMC:
PMID:
The Origin and Evolution of G Protein-Coupled Receptor Kinases
Arcady Mushegian, Vsevolod V. Gurevich, Eugenia V. Gurevich
G protein-coupled receptor (GPCR) kinases (GRKs) play key role in homologous desensitization of GPCRs. GRKs phosphorylate activated receptors, promoting high affinity binding of arrestins, which precludes G protein coupling. Direct binding to active GPCRs activates GRKs, so that they selectively phosphorylate only the activated form of the receptor regardless of the accessibility of the substrate peptides within it and their Ser/Thr-containing sequence. Mammalian GRKs were classified into three main lineages, but earlier GRK evolution has not been studied.Here we show that GRKs emerged at the early stages of eukaryotic evolution via an insertion of a kinase similar to ribosomal protein S6 kinase into a loop in RGS domain. GRKs in Metazoa fall into two clades, one including GRK2 and GRK3, and the other consisting of all remaining GRKs, split into GRK1-GRK7 lineage and GRK4-GRK5-GRK6 lineage in vertebrates. One representative of each of the two ancient clades is found as early as placozoan Trichoplax adhaerens.Several protists, two oomycetes and unicellular brown algae have one GRK-like protein, suggesting that the insertion of a kinase domain into the RGS domain preceded the origin of Metazoa. The two GRK families acquired distinct structural units in the N- and C-termini responsible for membrane recruitment and receptor association.Thus, GRKs apparently emerged before animals and rapidly expanded in true Metazoa, most likely due to the need for rapid signalling adjustments in fast-moving animals.
