Scaffolding proteins in G-protein signaling

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.

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.

Figure 2

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

Figure 3

Signaling from the Gα₁₃-radixin complex.

Figure 4

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

Figure 5

Scaffolding proteins that link subunits of heterotrimeric G proteins with MAP kinase cascade. A, The role of Ste5 in the mating signaling in yeast. B, Signaling complex assembled by KSR1, leading to ERK activation. C, Signaling complex assembled by JLP, leading to activation of JNK (or p38, see discussion in the main text). LPA, lysophosphatidic acid; RA, retinoic acid.