G蛋白偶聯受體激酶(GRKs)對GPCR的同源脫敏起著重要作用。受體被GRKs磷酸化激活後，會促進其與抑制蛋白高親和性結合，結果阻遏了與G蛋白的結合。直接結合活躍的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，而不顧這些受體內基質肽的可接近性或者他們含有絲氨酸蘇氨酸序列。
現在知道哺乳動物的GRKs可以分為三個主要的類別，但是早期的GRK進化機制卻不明確。最近，美國範德堡大學的Eugenia V. Gurevich等人做了一項關於G蛋白偶聯受體激酶的起源以及進化的研究，他們發現，GRKs明顯早於動物出現。相關論文發表於3月19日的美國《公共科學圖書館·綜合》（PLoS One）上。
Eugenia V. Gurevich指出：GRKs出現在真核生物進化早期，在那個時期，一個類似於核糖體蛋白S6激酶的激酶結構插入到了RGS結構域的一個環狀結構裡，結果形成了GRKs。GRKs在多細胞動物中形成了兩個分支，一個分支包括GRK2和GRK3，另一個包括剩下所有的GRKs。在脊椎動物中，GRKs則主要分為GRK1-GRK7和GRK4-GRK5-GRK6兩大類。兩種古分支中的一種,被發現早在絲盤蟲時期便已存在。幾種原生生物，兩種卵菌類和單細胞褐藻含有一種GRK樣的蛋白，這表明早在多細胞生物起源之前，激酶結構便已插入到RGS結構域。兩種GRK家族在N端以及C端獲得了不同的結構單元，而這些結構單元主要負責細胞膜的招募和受體的偶聯。
因此，研究結果表明，GRKs明顯早於動物出現，並快速的在後生動物中擴散，當然，這很可能是由於快速運動的動物需要對信號迅速調節所致。（生物谷Deepblue編譯）
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.