The betagamma subunit of heterotrimeric G proteins interacts with RACK1 and two other WD repeat proteins.

Dell EJ, Connor J, Chen S, Stebbins EG, Skiba NP, Mochly-Rosen D, Hamm HE
J Biol Chem. 2002 277 (51): 49888-95

PMID: 12359736 · DOI:10.1074/jbc.M202755200

A yeast two-hybrid approach was used to discern possible new effectors for the betagamma subunit of heterotrimeric G proteins. Three of the clones isolated are structurally similar to Gbeta, each exhibiting the WD40 repeat motif. Two of these proteins, the receptor for activated C kinase 1 (RACK1) and the dynein intermediate chain, co-immunoprecipitate with Gbetagamma using an anti-Gbeta antibody. The third protein, AAH20044, has no known function; however, sequence analysis indicates that it is a WD40 repeat protein. Further investigation with RACK1 shows that it not only interacts with Gbeta(1)gamma(1) but also unexpectedly with the transducin heterotrimer Galpha(t)beta(1)gamma(1). Galpha(t) alone does not interact, but it must contribute to the interaction because the apparent EC(50) value of RACK1 for Galpha(t)beta(1)gamma(1) is 3-fold greater than that for Gbeta(1)gamma(1) (0.1 versus 0.3 microm). RACK1 is a scaffold that interacts with several proteins, among which are activated betaIIPKC and dynamin-1 (1). betaIIPKC and dynamin-1 compete with Gbeta(1)gamma(1) and Galpha(t)beta(1)gamma(1) for interaction with RACK1. These findings have several implications: 1) that WD40 repeat proteins may interact with each other; 2) that Gbetagamma interacts differently with RACK1 than with its other known effectors; and/or 3) that the G protein-RACK1 complex may constitute a signaling scaffold important for intracellular responses.

MeSH Terms (33)

3T3 Cells Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Blotting, Western Cytoplasm Dimerization DNA Mutational Analysis Dose-Response Relationship, Drug Dynamin I Dyneins Glutathione Transferase GTP-Binding Proteins Heterotrimeric GTP-Binding Proteins Humans Isoenzymes Mice Models, Molecular Molecular Sequence Data Mutation Neoplasm Proteins Precipitin Tests Protein Binding Protein Kinase C Protein Kinase C beta Protein Structure, Secondary Protein Structure, Tertiary Receptors, Cell Surface Receptors for Activated C Kinase Sequence Homology, Amino Acid Signal Transduction Two-Hybrid System Techniques

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