title: Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP.
abstract: Long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse involves interacting signaling components, including calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhibitor of protein phosphatase-1 (PP1), substituted for cAMP pathway activation in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation of endogenous inhibitor-1 and a decrease in PP1 activity. This stimulation also increased phosphorylation of CaMKII at Thr286 and Ca2+-independent CaMKII activity in a cAMP-dependent manner. The blockade of LTP by a CaMKII inhibitor was not overcome by thiophosphorylated inhibitor-1. Thus, the cAMP pathway uses PP1 to gate CaMKII signaling in LTP.
authors.affiliation: Bronx VA Medical Center and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. rb2@doc.mssm.edu
authors.forename: R D
authors.initials: RD
authors.lastname: Blitzer
authors.forename: J H
authors.initials: JH
authors.lastname: Connor
authors.forename: G P
authors.initials: GP
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Shenolikar
authors.forename: R
authors.initials: R
authors.lastname: Iyengar
authors.forename: E M
authors.initials: EM
authors.lastname: Landau
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D013873:Thionucleotides; C021042:protein phosphatase inhibitor-1; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1