G protein-coupled receptor kinases: from molecules to diseases.

Abstract

THE 2014 FASEB SCIENCE Research Conference (SRC) on G Protein-Coupled Receptor Kinases: From Molecules to Diseases focused on recent advances in understanding the biochemistry of G protein-coupled receptor kinases (GRKs), their physiologic functions, and roles in pathologic conditions. GRKs are key regulators that, together with arrestins, determine the rate and extent of homologous desensitization of G protein-coupled receptors (GPCRs). GPCRs mediate responses to hormones and neurotransmitters inmultiple tissues and cell types and are targetedby many drugs. Therefore, proteins regulating GPCR signaling are critical for a variety of diseases and represent important therapeutic targets. Recent seminal discoveries attracted attention to novel aspects of GRKbiology, such as regulation of non-GPCR receptors and control of GPCR signaling in a phosphorylation-independent manner. This meeting brought together researchers studying varying aspects of GRK biology in this rapidly expanding field, from structural biologists to physiologists and physicianscientists.Thediscussionsbroadenedourunderstandingof fundamental functions of these exciting proteins and facilitated collaborations. The interdisciplinary nature of the meeting stems from appreciation that only joint effort of investigators studying the GRK action in different model systems will overcome remaining challenges in the GRK field andwill allow researchers to fully exploit the potential of GRKs as therapeutic targets. GPCRs are the largest superfamily of signaling proteins, with several hundred subtypes in all mammalian species. These receptors share a 7-transmembrane span structure and transmit the signal of agonist binding to the cell surface receptor in uniform manner via activation of intracellular heterotrimeric G proteins, as the name implies. The GPCR family occupies a position of extraordinary importance in physiology and medicine, not only because GPCRs control every aspect of physiological function but also because GPCRs are targeted by a large percentage of clinically used drugs. It is not surprising that GPCR signaling is under strict control viamultiplemechanisms.One Attendees of the FASEB Science Research Conference: G Protein-Coupled Receptor Kinases: From Molecules to Diseases (June 8–13, 2014) in Steamboat Springs, CO, USA.