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.

scholarly journals Fungal G-Protein-Coupled Receptors: A Promising Mediator of the Impact of Extracellular Signals on Biosynthesis of Ochratoxin A

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Gao ◽  
Xinge Xu ◽  
Kunlun Huang ◽  
Zhihong Liang
Keyword(s):  
G Protein ◽  
Ochratoxin A ◽  
G Protein Coupled Receptors ◽  
Aspergillus Ochraceus ◽  
Transmembrane Receptors ◽  
Environmental Signals ◽  
Extracellular Signals ◽  
Fungal Biology ◽  
The Impact ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) are transmembrane receptors involved in transducing signals from the external environment inside the cell, which enables fungi to coordinate cell transport, metabolism, and growth to promote their survival, reproduction, and virulence. There are 14 classes of GPCRs in fungi involved in sensing various ligands. In this paper, the synthesis of mycotoxins that are GPCR-mediated is discussed with respect to ligands, environmental stimuli, and intra-/interspecific communication. Despite their apparent importance in fungal biology, very little is known about the role of ochratoxin A (OTA) biosynthesis by Aspergillus ochraceus and the ligands that are involved. Fortunately, increasing evidence shows that the GPCR that involves the AF/ST (sterigmatocystin) pathway in fungi belongs to the same genus. Therefore, we speculate that GPCRs play an important role in a variety of environmental signals and downstream pathways in OTA biosynthesis. The verification of this inference will result in a more controllable GPCR target for control of fungal contamination in the future.

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 Membrane-associated periodic skeleton is a signaling platform for RTK transactivation in neurons

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. 929-934 ◽  
Author(s):  
Ruobo Zhou ◽  
Boran Han ◽  
Chenglong Xia ◽  
Xiaowei Zhuang
Keyword(s):  
Tyrosine Kinases ◽  
Super Resolution ◽  
Erk Signaling ◽  
Extracellular Signal Regulated Kinase ◽  
Rtk Signaling ◽  
Extracellular Signal ◽  
Extracellular Stimuli ◽  
Resolution Imaging ◽  
G Protein Coupled

Actin, spectrin, and related molecules form a membrane-associated periodic skeleton (MPS) in neurons. The function of the MPS, however, remains poorly understood. Using super-resolution imaging, we observed that G protein–coupled receptors (GPCRs), cell adhesion molecules (CAMs), receptor tyrosine kinases (RTKs), and related signaling molecules were recruited to the MPS in response to extracellular stimuli, resulting in colocalization of these molecules and RTK transactivation by GPCRs and CAMs, giving rise to extracellular signal–regulated kinase (ERK) signaling. Disruption of the MPS prevented such molecular colocalizations and downstream ERK signaling. ERK signaling in turn caused calpain-dependent MPS degradation, providing a negative feedback that modulates signaling strength. These results reveal an important functional role of the MPS and establish it as a dynamically regulated platform for GPCR- and CAM-mediated RTK signaling.

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