SPECIFIC ACTIVATION OF GS BY SYNTHETIC PEPTIDES CORRESPONDING TO AN INTRACELLULAR LOOP OF THE BETA-ADRENERGIC-RECEPTOR

Peptides corresponding to the amino acid sequence of the hamster beta-2-adrenergic receptor (beta-2-AR) were synthesized and their ability to activate purified G-proteins determined. Two peptides, comprising the N- and C-terminal 15 amino acids of the putative third intracellular loop region of the beta-2-AR were found to activate the G-protein G(s) but not to activate a preparation of G(i)/G(o). Other peptides corresponding to the internal portions of this loop and the C-terminal tail region failed to activate either G-protein. The presence of phospholipid vesicles was required for this activation. The observation that peptides with sequences corresponding to the ends of the third intracellular loop of the beta-AR can specifically activate G(s) confirms the results of previous mutagenesis studies on the receptor and demonstrates that the secondary structure conferred by the amino acid sequences in these regions is sufficient for the activation of G-proteins.