Resolution of a signal transfer region from a general binding domain in gbeta for stimulation of phospholipase C-beta2.
Signaling by guanine nucleotide-binding proteins (G proteins) involves sequential protein-protein interactions. G protein-betagamma subunit (Gbetagamma) interactions with phospholipase C-beta2 (PLC-beta2) were studied to determine if all Gbeta contacts are required for signaling. A peptide encoding Gbeta amino acid residues 86 to 105 stimulated PLC-beta2. Six residues (96 to 101) within this sequence could transfer signals and thus constitute a core signal transfer region. Another peptide, encoding Gbeta amino acid residues 115 to 135, did not substantially stimulate PLC-beta2 by itself but inhibited Gbetagamma stimulation, indicating that residues 115 to 135 constitute a general binding domain. Resolution of signal transfer regions from general binding domains indicates that all protein-protein contacts are not required for signal transfer and that it may be feasible to synthesize agonists and antagonists that regulate intracellular signal flow.
Buck
E
E
Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Li
J
J
Chen
Y
Y
Weng
G
G
Scarlata
S
S
Iyengar
R
R
D019943:Amino Acid Substitution; D001665:Binding Sites; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D054799:Phospholipase C beta; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins