Resolution of a Signal Transfer Region from a General Binding Domain in Gβ for Stimulation of Phospholipase C-β2

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Science  26 Feb 1999:
Vol. 283, Issue 5406, pp. 1332-1335
DOI: 10.1126/science.283.5406.1332

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Signaling by guanine nucleotide–binding proteins (G proteins) involves sequential protein-protein interactions. G protein–βγ subunit (Gβγ) interactions with phospholipase C–β2 (PLC-β2) were studied to determine if all Gβ contacts are required for signaling. A peptide encoding Gβ amino acid residues 86 to 105 stimulated PLC-β2. Six residues (96 to 101) within this sequence could transfer signals and thus constitute a core signal transfer region. Another peptide, encoding Gβ amino acid residues 115 to 135, did not substantially stimulate PLC-β2 by itself but inhibited Gβγ 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.

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