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 2AR) 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 2AR were found to activate the G-protein Gs but not to activate a preparation of Gi/Go. 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 Gs 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.
Cheung
A H
AH
Department of Molecular Pharmacology and Biochemistry, Merck, Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
Huang
R R
RR
Graziano
M P
MP
Strader
C D
CD
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides; D011487:Protein Conformation; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000737:chemistry
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D014862:Wasp Venoms; C037500:mastoparan; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins