G Protein-Coupled Receptor Kinases (2016) Pdf Free Download

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Features of G Protein-Coupled Receptor Kinases (2016) PDF free download:

The signaling by most G protein-coupled receptors (GPCRs) is regulated by a conserved two-step mechanism: phosphorylation of active receptor by G protein-coupled receptor kinases (GRKs) followed by specifi c binding of an arrestin protein to the active phosphoreceptor. Arrestin binding blocks further coupling of the receptor to G proteins, promotes the recruitment of the complex to coated pits for internalization, and initiates a second, G protein-independent round of signaling. Whereas GPCRs, G proteins, and arrestins are getting a lot of attention, GRKs remain underestimated and under-investigated players in the regulation of GPCR signaling. For example, in recent years, biased GPCR signaling, i.e., differential signaling via G protein- and arrestin-dependent pathways, has been extensively investigated in the hope of designing GPCR-targeting drugs with fewer side effects. However, for a ligand to be biased toward arrestins, it must be biased toward GRKs fi rst due to the fact that GRK phosphorylation in most cases is necessary for high- affi nity arrestin binding. GRKs have numerous other functions in addition to phosphorylating GPCRs, some of which do and some do not require kinase activity. In this book, we include up-todate descriptions of known GRK-dependent mechanisms, both associated with GPCR functions and receptor-independent. The chapters cover a wide range of studies from invertebrates to humans. Comprehensive mechanistic elucidation of GRK functions and their regulation in cells is necessary for a better understanding of cell biology, as well as for devising novel research approaches and therapeutic strategies.

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