Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling

Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling

G protein-coupled receptors (GPCRs) are recycled via a sequence-dependent pathway that is spatially and biochemically distinct from bulk recycling. Why there are two distinct recycling pathways from the endosome is a fundamental question in cell biology. In this study, we show that the separation of these two pathways is essential for normal spatial encoding of GPCR signaling. The prototypical ...

G-protein Coupled Receptor Dimerization

A growing body of evidence suggests that GPCRs exist and function as dimers or higher oligomers. The evidence for GPCR dimerization comes from biochemical, biophysical and functional studies. In addition, researchers have shown the occurrence of heterodimerization between different members of the GPCR family. Two receptors can interact with each other to make a dimer through their extracellular...

A direct and functional interaction between the trimeric G protein Go and Rab5 in G proteincoupled receptor signaling

Modeling of G-protein-coupled receptor signaling pathways.

G-protein-coupled receptors (GPCRs)2 are the largest family of cell membrane receptors. An estimated 50% of current pharmaceuticals target GPCRs (1), suggesting that further increases in our understanding ofGPCRs and the signaling pathways they initiate will lead to new drug targets. Mathematical and computationalmodeling (here, simply “modeling”) has a substantial history in modern biology and...

G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits.

The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals. The presence of increased levels of GRK2 in human embryonic kidney (HEK) 293 cells produced a significant reduction of the extracellular signal-regulated kinase (ERK) response to CC...