This review describes the present knowledge of the different mechanisms of ERK activation downstream of GPCRs and our present understanding of receptor-dependent and -independent MAPK activation cascades.

G protein-coupled receptors mediate two functionally distinct pathways of tyrosine phosphorylation in Rat 1a fibroblasts. Shc phosphorylation and receptor endocytosis correlate with activation of ERK kinases.

Oct 26, 2022 · G-protein-coupled receptors (GPCRs), the largest family of signalling receptors, as well as important drug targets, are known to activate extracellular-signal-regulated kinase (ERK)—a...

4 days ago · G protein-coupled receptors (GPCRs) are activated by a wide variety of external stimuli. Upon receptor activation, the G protein exchanges GDP for GTP, causing the dissociation of the GTP-bound α and β/γ subunits and triggering diverse signaling cascades.

One of the major cellular effectors activated by GPCRs is extracellular signal-regulated kinase (ERK). Both G-protein and β-arrestin mediated signaling pathways can lead to ERK activation. However, depending on activation pathway, the subcellular …

Jan 1, 2018 · Activation of ERK specifically through the βγ subunits has been shown for Gαi-coupled GPCRs, such as the muscarinic, adrenergic, dopamine, adenosine, and LPA receptors, and an overexpression of Gβγ subunits was sufficient to increase the basal ERK activity in COS-7 cells (Faure et al., 1994).

The authors have developed a new high-throughput homogeneous assay platform for GPCR discovery as an alternative to current assays, which employs detection of phosphorylation of the key signaling molecule p42/44 MAP kinase (ERK 1/2).

Oct 24, 2023 · Over the last two decades, ERK1/2 have been the most intensely studied signaling proteins scaffolded by β-arrestins. Here, we demonstrate that β-arrestins play an active role in allosterically modulating ERK kinase activity in vitro and within intact cells.

Jan 1, 2010 · Adrenergic receptors on cardiac fibroblasts were manipulated to examine the role of arrestin in the spatiotemporal regulation of ERK1/2 MAPK signaling. We show a general mechanism in which arrestin activation by one GPCR is capable of regulating signaling originating from another GPCR.

These data suggest that the C-terminal tail of a GPCR, by determining the stability of the receptor-β-arrestin complex, controls the extent of β-arrestin-bound ERK activation, and influences both the subcellular localization of activated ERK and the physiologic consequences of ERK activation.