Resolution of a signal transfer region from a general binding domain in Gβ for stimulation of phospholipase C-β2

Signaling by guanine nucleotide-binding proteins (G proteins) involves sequential protein-protein interactions. G protein-beta gamma subunit (G beta gamma) interactions with phospholipase C-beta 2 (PLC-beta 2) were studied to determine if all G beta contacts are required for signaling. A peptide encoding G beta amino acid residues 86 to 105 stimulated PLC-beta 2. Six residues (96 to 101) within this sequence could transfer signals and thus constitute a core signal transfer region. Another peptide, encoding G beta amino acid residues 115 to 135, did not substantially stimulate PLC-beta 2 by itself but inhibited G beta gamma 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 flaw.