While different orientations have been tested, in our hands, LgBiT-N-GRK/GPCR-C-SmBiT is the combination which yields the highest specific signal to background readouts. This technique allows to systematically profile the selectivity of a single GPCR for the seven GRKs (Fig. 2, Fig. 3A)...
Gln l-glutamine GRK GPCR kinase MKP-1 MAPK phosphatase-1 siRNA small interfering RNA Introduction Itch is a common symptom of skin diseases. It also occurs in some systemic diseases such as inflammatory skin diseases, systemic metabolic, and neurological disorders (Ikoma et al., 2006, Yosipovitc...
we anticipate generation of β-arrestin-biased ligands to be mechanistically challenging for the subgroup of GPCRs exclusively regulated by GRK2/3, but achievable for GRK5/6-regulated receptors, that do not demand liberated Gβγ. Accordingly, GRK specificity...
This was independent of the source of free Gβγ and observable for Gs-, Gi- and Gq-coupled GPCRs. Thus, β-arrestin interaction for GRK2/3-regulated receptors is inseparably connected with G protein activation. We outline a theoretical framework of how GRK dependence on free Gβγ can ...
grk structure mechanisms of activation and interactions with gpcrspartii
The G protein-coupled receptor kinase (GRK) interactome: role of GRKs in GPCR regulation and signaling. Biochim Biophys Acta. 2007;1768:913-922.Ribas, C, Penela, P, Murga, C, Salcedo, A, Garcia-Hoz, C, Jurado-Pueyo, M, Aymerich, I, and Mayor, F. 2007. "The G Protein-Coupled ...
As proof of concept, five prototypical GPCRs (MOP, C5a1, D1, SST2, CB2) were treated with different agonizts and antagonists, and concentration-response curves were generated. We then extended our approach to establish selective cellular GPCR kinase (GRK) inhibitor assays, which led to the ...