A region of adenylyl cyclase 2 critical for regulation by G protein beta gamma subunits.
Receptor-mediated activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) results in the dissociation of alpha from beta gamma subunits, thereby allowing both to regulate effectors. Little is known about the regions of effectors required for recognition of G beta gamma. A peptide encoding residues 956 to 982 of adenylyl cyclase 2 specifically blocked G beta gamma stimulation of adenylyl cyclase 2, phospholipase C-beta 3, potassium channels, and beta-adrenergic receptor kinase as well as inhibition of calmodulin-stimulated adenylyl cyclases, but had no effect on interactions between G beta gamma and G alpha o. Substitutions in this peptide identified a functionally important motif, Gln-X-X-Glu-Arg, that is also conserved in regions of potassium channels and beta-adrenergic receptor kinases that participate in G beta gamma interactions. Thus, the region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from G beta gamma.
Chen
J
J
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029, USA.
DeVivo
M
M
Dingus
J
J
Harry
A
A
Li
J
J
Sui
J
J
Carty
D J
DJ
Blank
J L
JL
Exton
J H
JH
Stoffel
R H
RH
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000502:physiology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D010446:Peptide Fragments; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D006160:Guanosine Triphosphate; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases