G protein β subunit types differentially interact with a muscarinic receptor but not adenylyl cyclase type II or phospholipase C-β2/3

In comparison with the alpha subunit of G proteins, the role of the beta subunit in signaling is less well understood. During the regulation of effecters by the beta gamma complex, it is known that the beta subunit contacts effecters directly, whereas the role of the beta subunit is undefined in receptor-G protein interaction, Among the five G protein beta subunits known, the beta (4) subunit type is the least studied. me compared the ability of beta gamma complexes containing beta (4) and the well characterized beta (1) to stimulate three different effecters: phospholipase C-beta2, phospholipase C-beta3, and adenylyl cyclase type II. beta (4)gamma (2) and beta (1)gamma (2) activated all three of these effecters: with equal efficacy. However, nucleotide exchange in a G protein constituting alpha (o)beta (4)gamma (2) mas stimulated significantly more by the M2 muscarinic receptor compared with alpha (o)beta (1)gamma (2). Because alpha (o) forms heterotrimers with beta (4)gamma (2) and beta (1)gamma (2) equally well, these results show that the beta subunit type plays a direct role in the receptor activation of a G protein.