Regulation of the GABA receptor complex by a phosphorylation mechanism.
GABA- modulin , a regulatory component of the GABA/benzodiazepine receptor complex, is phosphorylated by cyclic-AMP-, Ca/calmodulin-, and Ca/phospholipid-dependent protein kinases at distinct sites in the molecule. Phosphorylation of GM by the cyclic-AMP-dependent process results in a complete loss of GM inhibitory activity on specific 3H-GABA binding to synaptic membrane recognition sites. The effect of the Ca2+-dependent phosphorylation, dependent on CaM or PS, of GM is presently unknown but may involve a synergistic or antagonistic action on the cyclic-AMP-dependent phosphorylation. Alternatively, the Ca2+-dependent protein kinases may regulate another function of GM, perhaps its postulated role as a coupler of the GABA/benzodiazepine recognition sites. The results of these experiments strongly implicate a role for protein phosphorylation in the regulation or modulation of GABA receptor function, and such a mechanism may be extrapolated to other neurotransmitter receptor complexes.
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000502:physiology; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D027361:Organic Anion Transporters; D010718:Phosphatidylserines / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013570:Synaptic Membranes / Q000378:metabolism
D002147:Calmodulin; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D000242:Cyclic AMP; D011494:Protein Kinases; D002118:Calcium