Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways alongside the G-protein dependent pathways. ERK activation pathways can be categorised into two main sub-pathways based on their subcellular localisation Minireview: targeting GPCR activated ERK pathways for drug discovery. Spatiotemporal regulation of the p42/p44 MAPK pathway. Biology of the Cell, 93(1‐2), 71-79.

Learn about communication between GPCRs and PKA, Class F GPCR Smoothened & the Hedgehog signaling pathway

September 2022 "Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid scramblases as evinced after their reconstitution into liposomes. Yet phospholipid scrambling is not detectable in the resting plasma membrane of mammalian cells that is replete with GPCRs. We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids. Our previous Markov State Model (MSM) analysis of molecular dynamics simulations of membrane-embedded opsin indicated that phospholipid headgroups traverse a dynamically revealed hydrophilic groove between transmembrane helices (TM) 6 and 7 while their tails remain in the bilayer. Here, we present comparative MSM analyses of 150-μs simulations of opsin in cholesterol-free and cholesterol-rich membranes. Our analyses reveal that cholesterol inhibits phospholipid scrambling by occupying the TM6/7 interface and stabilizing the closed groove conformation while itself undergoing flip-flop. This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane." Read more at the source #DrGPCR #GPCR #IndustryNews

Pharmacological inhibition of the lipid synthesis pathway by statins is a therapeutic approach to control Tennakoon , Waruna Thotamune , John L Payton , Ajith Karunarathne Tags HMG-CoA reductase , cholesterol , mevalonate pathway , optogenetics , prenylation , prenyltransferases , statin Source Contribute to the GPCR News

< GPCR News < GPCRs in Oncology and Immunology GPR56 signaling pathway network and its dynamics in the mining of the molecular events plausibly associated with GPR56 activity, we have constructed a signaling pathway others associated with Wnt, integrin, calcium signaling, growth factors, and inflammation signaling pathways We also considered intracellular and extracellular factors that may influence the activity of the pathway Raksha A Ganesh , Krishnan Venkataraman , Ravi Sirdeshmukh Tags GPR56 /ADGRG1 , Mesenchymal transition , Pathway

< GPCR News < GPCRs in Oncology and Immunology Context-dependent ciliary regulation of hedgehog pathway In the hedgehog pathway, bifunctional GLI transcription factors generate both GLI-activators (GLI-A) However, how these counterregulatory effectors coordinate cilia-regulated morphogenetic pathways is unclear Here we determined GLI-A/GLI-R requirements in phenotypes arising from lack of hedgehog pathway repression We studied hedgehog pathway repression by the GPCR GPR161, and the ankyrin repeat protein ANKMY2 that