title: Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase.
abstract: Activation of cAMP-dependent protein kinase (PKA) can enhance or reduce the function of neuronal GABAA receptors, the major sites of fast synaptic inhibition in the brain. This differential regulation depends on PKA-induced phosphorylation of adjacent conserved sites in the receptor beta subunits. Phosphorylation of beta 3 subunit-containing receptors at S408 and S409 enhanced the GABA-activated response, whereas selectively mutating S408 to alanine converted the potentiation into an inhibition, comparable to that of beta 1 subunits, which are phosphorylated solely on S409. These distinct modes of regulation were interconvertible between beta 1 and beta 3 subunits and depended upon the presence of S408 in either subunit. In contrast, beta 2 subunit-containing receptors were not phosphorylated or affected by PKA. Differential regulation by PKA of postsynaptic GABAA receptors containing different beta subunits may have profound effects on neuronal excitability.
authors: MRC Laboratory for Molecular Cell Biology, University College, London, UK.
authors: B J
authors: BJ
authors: McDonald
authors: A
authors: A
authors: Amato
authors: C N
authors: CN
authors: Connolly
authors: D
authors: D
authors: Benke
authors: S J
authors: SJ
authors: Moss
authors: T G
authors: TG
authors: Smart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007536:Isomerism; D051379:Mice; D009154:Mutation / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases