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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.


Signaling complexes assembled by TPR-repeat scaffolding proteins: TPR1 (A) and RACK1 (B). See main text for description.
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Figure 2: Signaling complexes assembled by TPR-repeat scaffolding proteins: TPR1 (A) and RACK1 (B). See main text for description.

Mentions: TPR1 was initially identified as a protein containing three TPR motifs, which interacts with the GAP domain of neurofibromin (NF1) [40]. It also interacts with and is a co-chaperone of Hsp70 [41,42]. TPR1 was found to interact with Gα16, as well as Gαq, Gαs, and to a much lesser extent with Gαi (but not Gα13 or Gαt), as well as with HA-Ras (but not Rho, Cdc42 and Rac) [43]. In the absence of Gα16, HA-Ras was found to bind to TPR1 preferentially in the activated conformation, however in the presence of Gα16 binding was similar for activated and inactive HA-Ras. Binding of Gα16 facilitated binding of HA-Ras to TPR1 and led to accumulation of the activated Ras (Fig. 2A), apparently by stabilizing the activated conformation, rather than by promoting GDP-GTP exchange. In contrast, binding of HA-Ras had no effect on the binding of Gα16. The physiological role of the formation of the Gα16-TPR1-Ras complex remains to be explored.


Scaffolding proteins in G-protein signaling.

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

Signaling complexes assembled by TPR-repeat scaffolding proteins: TPR1 (A) and RACK1 (B). See main text for description.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Signaling complexes assembled by TPR-repeat scaffolding proteins: TPR1 (A) and RACK1 (B). See main text for description.
Mentions: TPR1 was initially identified as a protein containing three TPR motifs, which interacts with the GAP domain of neurofibromin (NF1) [40]. It also interacts with and is a co-chaperone of Hsp70 [41,42]. TPR1 was found to interact with Gα16, as well as Gαq, Gαs, and to a much lesser extent with Gαi (but not Gα13 or Gαt), as well as with HA-Ras (but not Rho, Cdc42 and Rac) [43]. In the absence of Gα16, HA-Ras was found to bind to TPR1 preferentially in the activated conformation, however in the presence of Gα16 binding was similar for activated and inactive HA-Ras. Binding of Gα16 facilitated binding of HA-Ras to TPR1 and led to accumulation of the activated Ras (Fig. 2A), apparently by stabilizing the activated conformation, rather than by promoting GDP-GTP exchange. In contrast, binding of HA-Ras had no effect on the binding of Gα16. The physiological role of the formation of the Gα16-TPR1-Ras complex remains to be explored.

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.