PMID- 10195104
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20131121
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 1
IP  - 1
DP  - 1998 May
TI  - Adjacent phosphorylation sites on GABAA receptor beta subunits determine
      regulation by cAMP-dependent protein kinase.
PG  - 23-8
AB  - 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.
FAU - McDonald, B J
AU  - McDonald BJ
AD  - MRC Laboratory for Molecular Cell Biology, University College, London, UK.
FAU - Amato, A
AU  - Amato A
FAU - Connolly, C N
AU  - Connolly CN
FAU - Benke, D
AU  - Benke D
FAU - Moss, S J
AU  - Moss SJ
FAU - Smart, T G
AU  - Smart TG
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Receptors, GABA-A)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Cyclic AMP/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Enzyme Activation/physiology
MH  - Humans
MH  - Isomerism
MH  - Mice
MH  - Mutation/physiology
MH  - Patch-Clamp Techniques
MH  - Phosphorylation
MH  - Receptors, GABA-A/drug effects/genetics/*metabolism/physiology
MH  - Transfection
MH  - gamma-Aminobutyric Acid/pharmacology
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1038/223 [doi]
PST - ppublish
SO  - Nat Neurosci. 1998 May;1(1):23-8. doi: 10.1038/223.