Many receptors can activate multiple independent signal transduction pathways. Chang et al. have developed a method for creating membrane-permeable peptides to specifically disrupt individual signal transduction pathways to elucidate the role of each pathway in the generating the cellular responses. The peptides were directed to block the interactions of the G protein with the specific target effectors. Three systems were used to demonstrate the principle: (i) the selective disruption of signaling through Gq to phospholipase-Cβ by the serotonin receptor 5-HT2c, (ii) the selective disruption of signaling through Gβγ to mitogen-activated protein kinase by α2A adrenergic receptors, and (iii) the selective disruption of signaling through Gq to phospholipase-Cβ by the thrombin receptor. Additionally, their methods allow for modular synthesis of the membrane-permeable peptides, providing versatility, increased yield, and lower costs compared with other methods of peptide synthesis.
Chang, M., Zhang, L., Tam, J.P., and Sanders-Bush, E. (2000) Dissecting G protein-coupled receptor signaling pathways with membrane-permeable blocking peptides. J. Biol. Chem. 275: 7021-7029. [Abstract] [Full Text]