PT  - JOURNAL ARTICLE
AU  - Melanie J. Robbins
AU  - Andrew R. Calver
AU  - Alexander K. Filippov
AU  - Warren D. Hirst
AU  - Robert B. Russell
AU  - Martyn D. Wood
AU  - Shabina Nasir
AU  - Andrés Couve
AU  - David A. Brown
AU  - Stephen J. Moss
AU  - Menelas N. Pangalos
TI  - GABA<sub>B2</sub> Is Essential for G-Protein Coupling of the GABA<sub>B</sub> Receptor Heterodimer
AID  - 10.1523/JNEUROSCI.21-20-08043.2001
DP  - 2001 Oct 15
TA  - The Journal of Neuroscience
PG  - 8043--8052
VI  - 21
IP  - 20
4099  - http://www.jneurosci.org/content/21/20/8043.short
4100  - http://www.jneurosci.org/content/21/20/8043.full
SO  - J. Neurosci.2001 Oct 15; 21
AB  - GABAB receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABAB1and GABAB2, for functional expression. Whereas GABAB1 is capable of binding receptor agonists and antagonists, the role of each GABAB subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABAB2 that are critical for the coupling of GABAB receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABAB2 subunit in G-protein coupling of the GABAB receptor heterodimer. In addition, they provide evidence for a novel “sequential” GPCR signaling mechanism in which ligand binding to one heterodimer subunit can induce signal transduction through the second partner of a heteromeric complex.