G Protein beta subunit types differentially interact with a muscarinic receptor but not adenylyl cyclase type II or phospholipase C-beta 2/3.
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 effectors by the betagamma complex, it is known that the beta subunit contacts effectors 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. We compared the ability of betagamma complexes containing beta(4) and the well characterized beta(1) to stimulate three different effectors: 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 effectors with equal efficacy. However, nucleotide exchange in a G protein constituting alpha(o)beta(4)gamma(2) was 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.
Departments of Anesthesiology and Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Y
Y
Hou
V
V
Chang
A B
AB
Capper
R
R
Taussig
N
N
Gautam
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001704:Biopolymers; D017931:DNA Primers; D004789:Enzyme Activation; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D007527:Isoenzymes / Q000378:metabolism*; D008969:Molecular Sequence Data; D054799:Phospholipase C beta; D011485:Protein Binding; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D010738:Type C Phospholipases / Q000378:metabolism*
D001704:Biopolymers; D017931:DNA Primers; D007527:Isoenzymes; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases