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.

[1]  Christian Rosenmund,et al.  Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons , 1994, Nature.

[2]  L. Langeberg,et al.  Cloning and characterization of AKAP 95, a nuclear protein that associates with the regulatory subunit of type II cAMP-dependent protein kinase. , 1994, The Journal of biological chemistry.

[3]  P. Cohen,et al.  On target with a new mechanism for the regulation of protein phosphorylation. , 1993, Trends in biochemical sciences.

[4]  S. Elledge,et al.  The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. , 1993, Genes & development.

[5]  R. Cone,et al.  Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79. , 1992, The Journal of biological chemistry.

[6]  M. Murcko,et al.  Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506-calcineurin complex. , 1992, The Journal of biological chemistry.

[7]  T. Soderling,et al.  Characterization of the phosphatase activity of a baculovirus-expressed calcineurin A isoform. , 1992, Journal of Biological Chemistry.

[8]  I. Fraser,et al.  Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain. , 1992, The Journal of biological chemistry.

[9]  Y. You,et al.  Cloning and expression of an intron-less gene for AKAP 75, an anchor protein for the regulatory subunit of cAMP-dependent protein kinase II beta. , 1992, The Journal of biological chemistry.

[10]  S. Fields,et al.  The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Stuart L. Schreiber,et al.  Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes , 1991, Cell.

[12]  I. Fraser,et al.  Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif. , 1991, The Journal of biological chemistry.

[13]  J. Kofron,et al.  Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. , 1991, Biochemistry.

[14]  C. Klee,et al.  Serine/threonine phosphatases in the nervous system , 1991, Current Opinion in Neurobiology.

[15]  D. Bregman,et al.  Molecular characterization of bovine brain P75, a high affinity binding protein for the regulatory subunit of cAMP-dependent protein kinase II beta. , 1991, The Journal of biological chemistry.

[16]  John D. Scott,et al.  Immunocytochemical localization of the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase to postsynaptic structures in the rat brain , 1990, Brain Research.

[17]  T. Takeda,et al.  Evidence for a second isoform of the catalytic subunit of calmodulin-dependent protein phosphatase (calcineurin A). , 1989, Biochemical and biophysical research communications.

[18]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[19]  D. Bregman,et al.  High affinity binding protein for the regulatory subunit of cAMP-dependent protein kinase II-B. Cloning, characterization, and expression of cDNAs for rat brain P150. , 1989, The Journal of biological chemistry.

[20]  P. Cohen.  The structure and regulation of protein phosphatases. , 1989, Annual review of biochemistry.

[21]  E. Krebs,et al.  Identification of an inhibitory region of the heat-stable protein inhibitor of the cAMP-dependent protein kinase. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  U. Walter,et al.  High-affinity binding of the regulatory subunit (RII) of cAMP-dependent protein kinase to microtubule-associated and other cellular proteins. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Klee,et al.  Interaction of calmodulin with myosin light chain kinase and cAMP-dependent protein kinase in bovine brain. , 1981, The Journal of biological chemistry.

[24]  J. Wood,et al.  Immunocytochemical localization of calmodulin and a heat-labile calmodulin-binding protein (CaM-BP80) in basal ganglia of mouse brain , 1980, The Journal of cell biology.

[25]  P. Siekevitz,et al.  Presence of calmodulin in postsynaptic densities isolated from canine cerebral cortex. , 1979, The Journal of biological chemistry.

[26]  E. Krebs,et al.  Phosphorylation-dephosphorylation of enzymes. , 1979, Annual review of biochemistry.