Carboxyl Terminal Domain of G$_{\text{s}\alpha}$ Specifies Coupling of Receptors to Stimulation of Adenylyl Cyclase

• Published in: Science (American Association for the Advancement of Science) 1988-07, Vol.241 (4864), p.448-451
• Main Authors: Masters, Susan B., Sullivan, Kathleen A., Miller, R. Tyler, Beiderman, Barry, Lopez, Ninfa G., Ramachandran, J., Bourne, Henry R.
• Format: Article
• Language: English
• Subjects: Antiserum; Cell membranes; Chimeras; Complementary DNA; COS cells; Physiological regulation; Proteins; Receptors; Toxins; Viroids
• ISSN: 0036-8075; 1095-9203

The $\alpha $ subunits of G$_{\text{s}}$ and G$_{\text{i}}$ link different sets of hormone receptors to stimulation and inhibition, respectively, of adenylyl cyclase. A chimeric $\alpha _{\text{i}}/\alpha _{\text{s}}$ cDNA was constructed that encodes a polypeptide composed of the amino terminal 60% of an $\alpha _{\text{i}}$ chain and the carboxyl terminal 40% of $\alpha _{\text{s}}$. The cDNA was introduced via a retroviral vector into S49 cyc$^{-}$ cells, which lack endogenous $\alpha _{\text{s}}$. Although less than half of the hybrid $\alpha $ chain is derived from $\alpha _{\text{s}}$, its ability to mediate $\beta $-adrenoceptor stimulation of adenylyl cyclase matched that of the normal $\alpha _{\text{s}}$ polypeptide expressed from the same retroviral vector in cyc$^{-}$ cells. This result indicates that carboxyl terminal amino acid sequences of $\alpha _{\text{s}}$ contain the structural features that are required for specificity of interactions with the effector enzyme, adenylyl cyclase, as well as with the hormone receptor.