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Scaffolding proteins in G-protein signaling.

Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA - J Mol Signal (2007)

Bottom Line: A number of scaffolding proteins have been identified that regulate various facets of GPCR signaling.In this review, we summarize current knowledge concerning those scaffolding proteins that are known to directly bind heterotrimeric G proteins, and discuss the composition of the protein complexes they assemble and their effects on signal transduction.Emerging evidence about possible ways of regulation of activity of these scaffolding proteins is also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, College of Medicine, University of Illinois at Chicago, 909 S, Wolcott Ave, Chicago, Illinois 60612, USA. tvy@uic.edu.

ABSTRACT
Heterotrimeric G proteins are ubiquitous signaling partners of seven transmembrane-domain G-protein-coupled receptors (GPCRs), the largest (and most important pharmacologically) receptor family in mammals. A number of scaffolding proteins have been identified that regulate various facets of GPCR signaling. In this review, we summarize current knowledge concerning those scaffolding proteins that are known to directly bind heterotrimeric G proteins, and discuss the composition of the protein complexes they assemble and their effects on signal transduction. Emerging evidence about possible ways of regulation of activity of these scaffolding proteins is also discussed.

No MeSH data available.


The role of EBP50 (NERF) in downregulation of G protein signaling.
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Figure 4: The role of EBP50 (NERF) in downregulation of G protein signaling.

Mentions: EBP50 (ezrin-radixin-moesin-binding phosphoprotein 50, also termed NHERF1 for Na+-H+ exchanger regulatory factor 1) is a PDZ domain-containing scaffolding protein known to bind to a variety of proteins, including ERM proteins, channels, receptors, cytoskeletal elements, and cytoplasmic proteins (for a recent review, see [63]). EBP50 was found to interact with Gαq via its PDZ domains [64]. The interaction was more efficient with activated than with inactive form of Gαq; accordingly, stimulation of the thromboxane A2receptor (which is coupled to Gq) enhanced the Gαq-EBP50 interaction. EBP50 was also able to interact with Gαs, and stimulation of the β2-adrenergic receptor (coupled to Gαs) was found to promote EBP50 binding to Gαs. However, several other Gα tested (Gαi/o/t/z, Gα12/13, and Gα16) did not interact with EBP50. Sequestering of Gαq by EBP50 was found to interfere with the Gα-receptor interaction and to inhibit Gαq-dependent stimulation of PLCβ ([64]; Fig. 4). EBP50 is known to bind directly and to mediate recycling of a number of receptors [65,66]; it was also found to inhibit internalization of the thromboxane A2β receptor induced by Gαq [67]. One of the future challenges would be to establish whether, in addition to blocking Gα interactions with receptors and effectors, Gα-EBP50 interaction may functionally link Gαq and/or Gαs to other interacting partners of EBP50.


Scaffolding proteins in G-protein signaling.

Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA - J Mol Signal (2007)

The role of EBP50 (NERF) in downregulation of G protein signaling.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211295&req=5

Figure 4: The role of EBP50 (NERF) in downregulation of G protein signaling.
Mentions: EBP50 (ezrin-radixin-moesin-binding phosphoprotein 50, also termed NHERF1 for Na+-H+ exchanger regulatory factor 1) is a PDZ domain-containing scaffolding protein known to bind to a variety of proteins, including ERM proteins, channels, receptors, cytoskeletal elements, and cytoplasmic proteins (for a recent review, see [63]). EBP50 was found to interact with Gαq via its PDZ domains [64]. The interaction was more efficient with activated than with inactive form of Gαq; accordingly, stimulation of the thromboxane A2receptor (which is coupled to Gq) enhanced the Gαq-EBP50 interaction. EBP50 was also able to interact with Gαs, and stimulation of the β2-adrenergic receptor (coupled to Gαs) was found to promote EBP50 binding to Gαs. However, several other Gα tested (Gαi/o/t/z, Gα12/13, and Gα16) did not interact with EBP50. Sequestering of Gαq by EBP50 was found to interfere with the Gα-receptor interaction and to inhibit Gαq-dependent stimulation of PLCβ ([64]; Fig. 4). EBP50 is known to bind directly and to mediate recycling of a number of receptors [65,66]; it was also found to inhibit internalization of the thromboxane A2β receptor induced by Gαq [67]. One of the future challenges would be to establish whether, in addition to blocking Gα interactions with receptors and effectors, Gα-EBP50 interaction may functionally link Gαq and/or Gαs to other interacting partners of EBP50.

Bottom Line: A number of scaffolding proteins have been identified that regulate various facets of GPCR signaling.In this review, we summarize current knowledge concerning those scaffolding proteins that are known to directly bind heterotrimeric G proteins, and discuss the composition of the protein complexes they assemble and their effects on signal transduction.Emerging evidence about possible ways of regulation of activity of these scaffolding proteins is also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, College of Medicine, University of Illinois at Chicago, 909 S, Wolcott Ave, Chicago, Illinois 60612, USA. tvy@uic.edu.

ABSTRACT
Heterotrimeric G proteins are ubiquitous signaling partners of seven transmembrane-domain G-protein-coupled receptors (GPCRs), the largest (and most important pharmacologically) receptor family in mammals. A number of scaffolding proteins have been identified that regulate various facets of GPCR signaling. In this review, we summarize current knowledge concerning those scaffolding proteins that are known to directly bind heterotrimeric G proteins, and discuss the composition of the protein complexes they assemble and their effects on signal transduction. Emerging evidence about possible ways of regulation of activity of these scaffolding proteins is also discussed.

No MeSH data available.