Splice Variants of the α Subunit of the G Protein Gs Activate Both Adenylyl Cyclase and Calcium Channels

Signal transducing guanine nucleotide binding (G) proteins are heterotrimers with different α subunits that confer specificity for interactions with receptors and effectors. Eight to ten such G proteins couple a large number of receptors for hormones and neurotransmitters to at least eight different effectors. Although one G protein can interact with several receptors, a given G protein was thought to interact with but one effector. The recent finding that voltage-gated calcium channels are stimulated by purified G_s, which stimulates adenylyl cyclase, challenged this concept. However, purified G_s may have four distinct α -subunit polypeptides, produced by alternative splicing of messenger RNA. By using recombinant DNA techniques, three of the splice variants were synthesized in Escherichia coli and each variant was shown to stimulate both adenylyl cyclase and calcium channels. Thus, a single G protein α subunit may regulate more than one effector function.