GABAB2 is essential for G-protein coupling of the GABAB receptor heterodimer

被引：166

作者：

Robbins, MJ

Calver, AR

Filippov, AK

Hirst, WD

Russell, RB

Wood, MD

Nasir, S

Couve, A

Brown, DA

Moss, SJ

Pangalos, MN

机构：

[1] GlaxoSmithKline, Dept Neurol CEDD, Harlow CM19 5AW, Essex, England

[2] GlaxoSmithKline, Dept Psychiat CEDD, Harlow CM19 5AW, Essex, England

[3] GlaxoSmithKline, Bioinformat Res Grp, Harlow CM19 5AW, Essex, England

[4] UCL, Dept Pharmacol, London WC1E 6BT, England

[5] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England

来源：

JOURNAL OF NEUROSCIENCE | 2001年 / 21卷 / 20期

关键词：

GABA(B); GPCR; dimerization; signaling; G-protein coupling; receptor subunits;

D O I：

10.1523/JNEUROSCI.21-20-08043.2001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABA(B2) that are critical for the coupling of GABA(B) receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABA(B2) subunit in G-protein coupling of the GABA(B) 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.

引用

页码：8043 / 8052

页数：10

共 39 条

[11]

Filippov AK, 2000, J NEUROSCI, V20, P2867

[12] Role of the second and third intracellular loops of metabotropic glutamate receptors in mediating dual signal transduction activation [J].