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GABAB Is Coupled through GB2

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Science's STKE  05 Feb 2002:
Vol. 2002, Issue 118, pp. tw61-TW61
DOI: 10.1126/stke.2002.118.tw61

Heterodimerization among G-protein-coupled receptors (GPCRs) can result in different properties for the oligomeric receptors compared with those of either receptor alone. Duthey et al. determined that the GB2 subunit, but not the GB1 subunit, of the heterodimeric γ-amino butyric acid (GABA)B receptor was the subunit responsible for G protein activation of that obligate dimeric GPCR. Various combinations of heterodimeric receptors with mutations in residues predicted to be critical for G protein coupling were transfected into HEK 293 cells or primary cultured neurons. Only cells expressing mutations in Leu686 of the GB2 subunit showed decreased coupling to downstream effectors. The Leu686 mutant GB2-containing receptors exhibited normal ligand binding characteristics, suggesting that the signaling impairment was not the result of defective agonist binding. The requirement for a dimeric receptor with subunit-specific signaling functions is not unique. Another on this phenomenon occurs with the mouse thrombin receptors described by Gough.

B. Duthey, S. Caudron, J. Perroy, B. Bettler, L. Fagni, J.-P. Pin, L. Prézeau, A single subunit (GB2) is required for G-protein activation by the heterodimeric GABAB receptor. J. Biol. Chem. 277, 3236-3241 (2002). [Abstract] [Full Text]

N. R. Gough, Signal transduction pathways as targets for therapeutics. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/76/pe1.[Summary] [Full Text]

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