Publication Date:
1995-01-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coghlan, V M -- Perrino, B A -- Howard, M -- Langeberg, L K -- Hicks, J B -- Gallatin, W M -- Scott, J D -- DK09059/DK/NIDDK NIH HHS/ -- GM48231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jan 6;267(5194):108-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7528941" target="_blank"〉PubMed〈/a〉
Keywords:
A Kinase Anchor Proteins
;
*Adaptor Proteins, Signal Transducing
;
Amino Acid Sequence
;
Animals
;
Binding Sites
;
*Brain Chemistry
;
Calcineurin
;
Calmodulin-Binding Proteins/analysis/antagonists & inhibitors/*metabolism
;
Carrier Proteins/analysis
;
Cattle
;
Cells, Cultured
;
Cyclic AMP-Dependent Protein Kinases/analysis/*metabolism
;
Hippocampus/chemistry
;
Molecular Sequence Data
;
Neurites/chemistry
;
Phosphoprotein Phosphatases/analysis/antagonists & inhibitors/*metabolism
;
Phosphorylation
;
Proteins/*metabolism/pharmacology
;
Rats
;
Recombinant Proteins/pharmacology
;
Tacrolimus/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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