Cell-Specific Extracellular Signal-Regulated Kinase Activation by Multiple G Protein-Coupled Receptor Families in Hippocampus

2003 ◽  
Vol 63 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Jennifer L. Berkeley ◽  
Allan I. Levey
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Kinase Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
G Protein Coupled

scholarly journals Chemokine Production by G Protein-Coupled Receptor Activation in a Human Mast Cell Line: Roles of Extracellular Signal-Regulated Kinase and NFAT

2000 ◽  
Vol 165 (12) ◽  
pp. 7215-7223 ◽  
Author(s):  
Hydar Ali ◽  
Jasimuddin Ahamed ◽  
Cristina Hernandez-Munain ◽  
Jonathan L. Baron ◽  
Michael S. Krangel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Line ◽  
G Protein ◽  
Receptor Activation ◽  
Human Mast Cell ◽  
Chemokine Production ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mast Cell Line ◽  
G Protein Coupled

scholarly journals Multifaceted roles of β-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling

2003 ◽  
Vol 375 (3) ◽  
pp. 503-515 ◽  
Author(s):  
Sudha K. SHENOY ◽  
Robert J. LEFKOWITZ
Keyword(s):  
G Protein ◽  
Receptor Internalization ◽  
Adapter Proteins ◽  
Adapter Protein ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Membrane Spanning ◽  
G Protein Coupled ◽  
Adp Ribosylation Factor

β-Arrestins are cytosolic proteins that bind to activated and phosphorylated G-protein-coupled receptors [7MSRs (seven-membrane-spanning receptors)] and uncouple them from G-protein-mediated second messenger signalling pathways. The binding of β-arrestins to 7MSRs also leads to new signals via activation of MAPKs (mitogen-activated protein kinases) such as JNK3 (c-Jun N-terminal kinase 3), ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38 MAPKs. By binding to endocytic proteins [clathrin, AP2 (adapter protein 2), NSF (N-ethylmaleimide-sensitive fusion protein) and ARF6 (ADP-ribosylation factor 6)], β-arrestins also serve as adapters to link the receptors to the cellular trafficking machinery. Agonist-promoted ubiquitination of β-arrestins is a prerequisite for their role in receptor internalization, as well as a determinant of the differing trafficking patterns of distinct classes of receptors. Recently, β-arrestins have also been implicated as playing novel roles in cellular chemotaxis and apoptosis. By virtue of their ability to bind, in a stimulus-dependent fashion, to 7MSRs as well as to different classes of cellular proteins, β-arrestins serve as versatile adapter proteins that regulate the signalling and trafficking of the receptors.

scholarly journals Noncanonical scaffolding of Gαi and β-arrestin by G protein-coupled receptors

2019 ◽  
Author(s):  
Jeffrey S. Smith ◽  
Thomas F. Pack ◽  
Asuka Inoue ◽  
Claudia Lee ◽  
Xinyu Xiong ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Environmental Signals ◽  
Extracellular Signal Regulated Kinase ◽  
Intracellular Signals ◽  
Extracellular Signal ◽  
Extracellular Stimuli ◽  
Protein Isoform ◽  
Sense And Respond ◽  
G Protein Coupled

SummaryG-protein-coupled receptors (GPCRs) enable cells to sense and respond appropriately to hormonal and environmental signals, and are a target of ~30% of all FDA-approved medications. Canonically, each GPCR couples to distinct Gα proteins, such as Gαs, Gαi, Gαq or Gα12/13, as well as β-arrestins. These transducer proteins translate and integrate extracellular stimuli sensed by GPCRs into intracellular signals through what are broadly considered separable signalling pathways. However, the ability of Gα proteins to directly interact with β-arrestins to integrate signalling has not previously been appreciated. Here we show a novel interaction between Gαi protein family members and β-arrestin. Gαi:β-arrestin complexes were formed by all GPCRs tested, regardless of their canonical G protein isoform coupling, and could bind both GPCRs as well as the extracellular signal-regulated kinase (ERK). This novel paradigm of Gαi:β-arrestin scaffolds enhances our understanding of GPCR signalling.

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