Structure and Function of G-Protein-Coupled Receptor Kinases 1 and 7

  • Tivadar Orban
  • Krzysztof PalczewskiEmail author
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


The importance of G protein-coupled receptor (GPCR) kinases (GRKs) as regulators of GPCR signaling has been widely recognized. In humans, GRKs constitute a family of seven protein kinases involved in the phosphorylation and desensitization of agonist-activated GPCRs in many physiological processes. The GPCR desensitization process is initiated by GRKs, but involves several subsequent steps including arrestin capping of phosphorylated receptors. High-resolution crystal structures were determined for four members of the GRK family, i.e., GRK1, GRK2, GRK5, and GRK6. This allowed decoding of the molecular basis of GRK activation and interactions with GPCR substrates, as well as the GRK interactions with cellular membranes and inhibitors. Here, we focused on retinal GRKs, or photopigment kinases, rhodopsin kinase (GRK1), and GRK7, in the context of major general advances in the GRK field.

Key words

G protein-coupled receptors (GPCRs) Retinal G protein-coupled receptor kinases (GRKs) Visual signal transduction cascade OGUCHI disease GRK1–rhodopsin interaction Structures of retinal GRKs and inhibitors 





G protein-coupled receptors


G protein-coupled receptor kinases




Protein kinase A




Photoactivated rhodopsin



We thank Drs. Leslie T. Webster Jr., and members of Palczewski laboratory for helpful comments on this manuscript. This work was supported by funding from the National Institutes of Health EY009339 (KP), EY025451 (KP), the Arnold and Mabel Beckman Foundation (KP), the Canadian Institute for Advanced Research (CIFAR), and the Foundation Fighting Blindness (KP). K.P. is John H. Hord Professor of Pharmacology.


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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pharmacology, School of Medicine, Cleveland Center for Membrane and Structural BiologyCase Western Reserve UniversityClevelandUSA

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