Association of protein kinase A and protein phosphatase 2B with a common anchoring protein.
Specificity of protein kinases and phosphatases may be achieved through compartmentalization with preferred substrates. In neurons, adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic densities by association of its regulatory subunit with an A kinase anchor protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA, AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase and the phosphatase was established in neurites of cultured hippocampal neurons. The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.
Coghlan
V M
VM
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Perrino
B A
BA
Howard
M
M
Langeberg
L K
LK
Hicks
J B
JB
Gallatin
W M
WM
Scott
J D
JD
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry; D008969:Molecular Sequence Data; D016501:Neurites / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D011506:Proteins; D011994:Recombinant Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus