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Publication : Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell.

First Author  Shen A Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  1050
PubMed ID  29535304 Mgi Jnum  J:260750
Mgi Id  MGI:6149445 Doi  10.1038/s41467-018-03459-7
Citation  Shen A, et al. (2018) Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell. Nat Commun 9(1):1050
abstractText  G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in a broad range of physiological responses and disease states. Activated GPCRs can undergo agonist-induced phosphorylation by G protein receptor kinases (GRKs) and second messenger-dependent protein kinases such as protein kinase A (PKA). Here, we characterize spatially segregated subpopulations of beta2-adrenergic receptor (beta2AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric beta2ARs that undergo endocytosis, whereas PKA modifies dimeric beta2ARs that remain at the cell surface. In hippocampal neurons, PKA-phosphorylated beta2ARs are enriched in dendrites, whereas GRK-phosphorylated beta2ARs accumulate in soma, being excluded from dendrites in a neuron maturation-dependent manner. Moreover, we show that PKA-phosphorylated beta2ARs are necessary to augment the activity of L-type calcium channel. Collectively, these findings provide evidence that functionally distinct subpopulations of this prototypical GPCR exist in a single cell.
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