Molecular basis for two forms of the G protein that stimulates adenylate cyclase

Most cells contain two forms of the α subunit of the G protein (G(s)) that stimulates adenylate cyclase; their apparent molecular weights are 45,000 and 52,000. Two cDNAs that correspond to distinct mRNAs for the α subunit of G(s) have been cloned from a bovine adrenal library and sequenced. The sequences of the two cDNAs, designated pG(s)-1 and pG(s)-s, are identical except for a single stretch of 46 nucleotides in the coding region, where four are altered and 42 are deleted in pG(s)-s. Expression of pG(s)-s and pG(s)-1 in COS-m6 cells yields protein products with apparent molecular weights of 45,000 and 52,000, respectively, based on their mobility in sodium dodecyl sulfate-polyacrylamide gels. We conclude that pG(s)-s and pG(s)-1 encode the 45- and 52-kDa forms of G(sα), respectively, and propose that the mRNAs encoding these proteins arise from a single gene by internal alternative RNA splicing.