approximately Next, we investigated kinase activity (Fig.2c). Gαq-coupled GPCRs trigger the mitogen-activated protein kinase (MAPK) pathway and induce transcription through a serum responsive element (SRE)60. Therefore, we measured luciferase activity driven by an SRE reporter (Fig.2h). As a...
In the GPCR-activated pathway, the signal was found to be amplified at the successive steps of the pathway so that the effector molecules are highly expressed compared to ligands. This amplification effect was more pronounced when the respective genes encoding the particular proteins were associated ...
Finally, a more-detailed evaluation of the structural basis for coupling to distinct intracellular signaling components will aid in the development of drugs that engender pathway-specific, ligand-biased signaling. Together, the approaches outlined above should permit the rational design of biased drugs ...
(Figure 3). GPCRs that signal through the Gαqand Gαspathways tend to increase insulin secretion, whereas GPCRs that signal through the Gαipathway generally inhibit insulin secretion. It is important to remember, however, that GPCRs couple to a complex of Gαβγ, so activation of ...
15). We hypothesize that the observed conformations of the holoreceptor can activate a certain signaling pathway while the same conformations are inactive for the other signaling pathways and vice versa. This potential signaling bias opens new directions for further studies on aGPCRs. An ECR-...
The exact pathway the G proteins take when trafficking from the ER to the plasma membrane also remains unresolved. 4. Membrane lipids and their relevance for GPCR-related signaling If the only purpose of membranes were to form a molecular barrier and a support for proteins, then two simple ...
An important aim in cell biology has been to identify and to observe dynamic interactions between protein molecules, as they execute the reactions of a particular biochemical pathway. Concerning GPCRs, despite elucidating ligand binding and signaling, the knowledge and investigation of conformational chan...
MitogenicSignalingPathwaysInducedbyGProtein-CoupledReceptorsENRIQUEROZENGURT*DivisionofDigestiveDiseases,DepartmentofMedicine,DavidGe..
Here we briefly describe the four steps in the MSC procedure as in the flowchart of Fig. 1: Figure 1 Flowchart of the unsupervised, multi-level MSC network clustering algorithm. Full size imageStep 1 (simplification). The MSC algorithm identifies the closest neighbor of each node and records ...
1.A method for determining G-coupled protein cellular receptor (“GPCR”) activation, employing β-galactosidase enzyme fragment complementation using an enzyme acceptor fragment (“EA”) and an enzyme donor fragment (“ED”), comprising the steps of:(a) providing a first fusion protein comprising...