Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex.
Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.
Westphal
R S
RS
Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson Road, Portland, OR 97201, USA.
Tavalin
S J
SJ
Lin
J W
JW
Alto
N M
NM
Fraser
I D
ID
Langeberg
L K
LK
Sheng
M
M
Scott
J D
JD
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020035:Holoenzymes / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D014162:Transfection
D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D048868:Adaptor Proteins, Signal Transducing; C486537:Akap9 protein, rat; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D020035:Holoenzymes; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; C518603:protein kinase inhibitor peptide (5-24); D019319:Okadaic Acid; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases