Article

Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein

Vollum Institute, Oregon Health Sciences University, Portland, 97201, USA.
Science (Impact Factor: 33.61). 04/1996; 271(5255):1589-92. DOI: 10.1126/science.271.5255.1589
Source: PubMed

ABSTRACT

Multivalent binding proteins, such as the yeast scaffold protein Sterile-5, coordinate the location of kinases by serving as platforms for the assembly of signaling units. Similarly, in mammalian cells the cyclic adenosine 3',5'-monophosphate-dependent protein kinase (PKA) and phosphatase 2B [calcineurin (CaN)] are complexed by an A kinase anchoring protein, AKAP79. Deletion analysis and binding studies demonstrate that a third enzyme, protein kinase C (PKC), binds AKAP79 at a site distinct from those bound by PKA or CaN. The subcellular distributions of PKC and AKAP79 were similar in neurons. Thus, AKAP79 appears to function as a scaffold protein for three multifunctional enzymes.

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    • "For example mAKAP confers bi-directional control of ryanodine receptor phosphorylation during excitation–contraction (EC) coupling; AKAP18γ manages calcium reuptake through the SERCA2 pump and AKAP-Lbc directs the nuclear export of class 2 histone deacetylases in response to hypertrophic signals [16,20,565758596061626364. A common feature of these anchored signaling complexes is the ability to synchronize calcium and cAMP signaling pathways [15]. The AKAP79/150 family of anchoring proteins embodies this property through their capacity to direct protein kinase A (PKA), protein kinase C (PKC) and calcineurin toward selected substrates [11, 31]. In mouse ventricular myocytes it has been shown that AKAP150 targets its cohort of calcium and cAMP responsive enzymes to Ca V 1.2 channels [44]. "
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    • "AKAP79/150 (also know as AKAP5) is a family of three orthologs: murine AKAP150, bovine AKAP75 and human AKAP79 [5] [33]. It is a widely expressed anchoring protein that interacts with PKA, protein kinase C (PKC), the phosphatase calcineurin (CaN), calmodulin (CaM) as well as other signaling molecules [34] [35] [36]. "
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