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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.


Schematic representation of Gα12/Gα13-containing signaling complexes assembled by A-kinase anchoring proteins (AKAPs): AKAP-Lbc (A) and AKAP-110 (B). See main text for details and references.
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Figure 1: Schematic representation of Gα12/Gα13-containing signaling complexes assembled by A-kinase anchoring proteins (AKAPs): AKAP-Lbc (A) and AKAP-110 (B). See main text for details and references.

Mentions: AKAP-Lbc was identified as a PKA-anchoring protein highly expressed in the heart that also has a Rho-specific guanine nucleotide exchange (GEF) activity ([27,28] reviewed by [29]). It was shown to interact with Rho in the inactive GDP-bound or nucleotide free form, but not with activated GTP-bound Rho. AKAP-Lbc was found to mediate activation of Rho by mutationally activated Gα12 and, to a lesser extent, by Gα13, but not several other tested Gα [28]. Moreover, AKAP-Lbc was shown to interact with Gα12 and to mediate Gα12-dependent Rho activation by lysophosphatidic acid (LPA) receptor ([28]; Fig. 1A) and by α1 adrenergic receptor, in the latter case mediating cardiomyocyte hypertrophy [30]. Anchored PKA phosphorylates AKAP-Lbc, thus allowing binding of 14-3-3, which in turn inhibits its RhoGEF activity by interfering with the interaction between AKAP-Lbc and RhoA [31,32]. Inhibition of RhoGEF activity by 14-3-3 requires AKAP-Lbc oligomerization [33]. These findings imply that cellular cAMP levels would regulate sensitivity of Gα12-dependent signaling via AKAP-Lbc. AKAP-Lbc may also anchor PKCα, which might phosphorylate Rho or Rho GDP dissociation inhibitor (RhoGDI) although its precise role in the AKAP-Lbc complex is unknown [24].


Scaffolding proteins in G-protein signaling.

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

Schematic representation of Gα12/Gα13-containing signaling complexes assembled by A-kinase anchoring proteins (AKAPs): AKAP-Lbc (A) and AKAP-110 (B). See main text for details and references.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Schematic representation of Gα12/Gα13-containing signaling complexes assembled by A-kinase anchoring proteins (AKAPs): AKAP-Lbc (A) and AKAP-110 (B). See main text for details and references.
Mentions: AKAP-Lbc was identified as a PKA-anchoring protein highly expressed in the heart that also has a Rho-specific guanine nucleotide exchange (GEF) activity ([27,28] reviewed by [29]). It was shown to interact with Rho in the inactive GDP-bound or nucleotide free form, but not with activated GTP-bound Rho. AKAP-Lbc was found to mediate activation of Rho by mutationally activated Gα12 and, to a lesser extent, by Gα13, but not several other tested Gα [28]. Moreover, AKAP-Lbc was shown to interact with Gα12 and to mediate Gα12-dependent Rho activation by lysophosphatidic acid (LPA) receptor ([28]; Fig. 1A) and by α1 adrenergic receptor, in the latter case mediating cardiomyocyte hypertrophy [30]. Anchored PKA phosphorylates AKAP-Lbc, thus allowing binding of 14-3-3, which in turn inhibits its RhoGEF activity by interfering with the interaction between AKAP-Lbc and RhoA [31,32]. Inhibition of RhoGEF activity by 14-3-3 requires AKAP-Lbc oligomerization [33]. These findings imply that cellular cAMP levels would regulate sensitivity of Gα12-dependent signaling via AKAP-Lbc. AKAP-Lbc may also anchor PKCα, which might phosphorylate Rho or Rho GDP dissociation inhibitor (RhoGDI) although its precise role in the AKAP-Lbc complex is unknown [24].

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.