G蛋白偶聯(lián)受體激酶(GRKs)對(duì)GPCR的同源脫敏起著重要作用,。受體被GRKs磷酸化激活后,，會(huì)促進(jìn)其與抑制蛋白高親和性結(jié)合,，結(jié)果阻遏了與G蛋白的結(jié)合,。直接結(jié)合活躍的GPCRs可以激活GRKs,，所以GRKs往往選擇性的只磷酸化激活形式的受體,，而不顧這些受體內(nèi)基質(zhì)肽的可接近性或者他們含有絲氨酸蘇氨酸序列,。
現(xiàn)在知道哺乳動(dòng)物的GRKs可以分為三個(gè)主要的類別，但是早期的GRK進(jìn)化機(jī)制卻不明確,。最近,，美國(guó)范德堡大學(xué)的Eugenia V. Gurevich等人做了一項(xiàng)關(guān)于G蛋白偶聯(lián)受體激酶的起源以及進(jìn)化的研究，他們發(fā)現(xiàn),，GRKs明顯早于動(dòng)物出現(xiàn),。相關(guān)論文發(fā)表于3月19日的美國(guó)《公共科學(xué)圖書館·綜合》（PLoS One）上。
Eugenia V. Gurevich指出：GRKs出現(xiàn)在真核生物進(jìn)化早期,，在那個(gè)時(shí)期,，一個(gè)類似于核糖體蛋白S6激酶的激酶結(jié)構(gòu)插入到了RGS結(jié)構(gòu)域的一個(gè)環(huán)狀結(jié)構(gòu)里，結(jié)果形成了GRKs,。GRKs在多細(xì)胞動(dòng)物中形成了兩個(gè)分支,，一個(gè)分支包括GRK2和GRK3，另一個(gè)包括剩下所有的GRKs,。在脊椎動(dòng)物中,，GRKs則主要分為GRK1-GRK7和GRK4-GRK5-GRK6兩大類。兩種古分支中的一種,被發(fā)現(xiàn)早在絲盤蟲時(shí)期便已存在,。幾種原生生物,，兩種卵菌類和單細(xì)胞褐藻含有一種GRK樣的蛋白，這表明早在多細(xì)胞生物起源之前,，激酶結(jié)構(gòu)便已插入到RGS結(jié)構(gòu)域,。兩種GRK家族在N端以及C端獲得了不同的結(jié)構(gòu)單元，而這些結(jié)構(gòu)單元主要負(fù)責(zé)細(xì)胞膜的招募和受體的偶聯(lián)。
因此,，研究結(jié)果表明,，GRKs明顯早于動(dòng)物出現(xiàn)，并快速的在后生動(dòng)物中擴(kuò)散,，當(dāng)然,，這很可能是由于快速運(yùn)動(dòng)的動(dòng)物需要對(duì)信號(hào)迅速調(diào)節(jié)所致。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0033806
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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.
