Palczewski K
Department of Ophthalmology, University of Washington, School of Medicine, Seattle 98195-6485, USA.
Eur J Biochem. 1997 Sep 1;248(2):261-9. doi: 10.1111/j.1432-1033.1997.00261.x.
Six vertebrate protein kinases (G-protein-coupled receptor kinases; GRKs) that regulate the function of G-protein-coupled receptors (GPCRs) were recently cloned; several distinct properties set them apart from conventional second-messenger regulated protein kinases. It appears that GRKs bind GPCR* through two separate sites: a high-affinity site, which involves intracellular loops of the activated receptor, and the lower-affinity site, encompassing the phosphorylation region. The high-affinity interaction may involve complementary structural elements of GRKs and GPCRs* rather than precise amino acid alignment, thus allowing broad and overlapping specificities of these kinases, in spite of differences in the sequences of GPCRs. In addition, GRK structures are modified by several posttranslational modifications, including phosphorylation, autophosphorylation, prenylation, carboxymethylation, and palmitoylation, probably affecting properties of these enzymes. While GRKs phosphorylate and inactivate receptor molecules which are engaged in G-protein activation, controversy surrounds whether GRKs might be activated and phosphorylate unstimulated GPCRs, leading to a desensitization of a larger population of the receptors. In this review, mechanistic aspects of GPCR* phosphorylation related to the distinct properties, regulation and modes of action of GRKs are described.
最近克隆出了六种调节G蛋白偶联受体（GPCR）功能的脊椎动物蛋白激酶（G蛋白偶联受体激酶；GRK）；它们的一些独特特性使其有别于传统的第二信使调节蛋白激酶。GRK似乎通过两个独立的位点与GPCR结合：一个高亲和力位点，涉及活化受体的细胞内环，以及一个低亲和力位点，包括磷酸化区域。高亲和力相互作用可能涉及GRK和GPCR的互补结构元件，而不是精确的氨基酸比对，因此尽管GPCR的序列存在差异，这些激酶仍具有广泛且重叠的特异性。此外，GRK的结构会被多种翻译后修饰所改变，包括磷酸化、自磷酸化、异戊二烯化、羧甲基化和棕榈酰化，这些修饰可能会影响这些酶的特性。虽然GRK会使参与G蛋白激活的受体分子磷酸化并使其失活，但对于GRK是否可能被激活并使未受刺激的GPCR磷酸化，从而导致更多受体脱敏，仍存在争议。在这篇综述中，将描述与GRK的独特特性、调节和作用模式相关的GPCR*磷酸化的机制方面。
