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1 University of Iowa, Iowa City, United States
2 Internal Medicine, University of Iowa, Iowa, United States
3 Biochemistry and Molecualr Biology, Univ. of Maryland School of Medicine, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: peter-mohler{at}uiowa.edu.
PP2A is a multifunctional protein phosphatase with critical roles in excitable cell signaling. In the heart, PP2A function is linked with modulation of beta-adrenergic signaling, and has been suggested to regulate key ion channels and transporters including Na/Ca exchanger, ryanodine receptor, inositol 1,4,5 trisphosphate receptor, and Na/K ATPase. While many of the functional roles and molecular targets for PP2A in heart are known, little is established regarding the cellular pathways that localize specific PP2A isoform activities to subcellular sites. We report that the PP2A regulatory subunit B56 alpha is a binding partner for ankyrin-B, an adapter protein required for normal subcellular localization of Na/Ca exchanger, Na/K ATPase, and InsP3 receptor. Ankyrin-B and B56
are co-localized and co-immunoprecipitate in primary cardiomyocytes. Using multiple strategies, we identify the structural requirements on B56 for ankyrin-B association as a thirteen residue motif in the B56 C-terminus not present in other B56 family polypeptides. Finally, we report that reduced ankyrin-B expression in primary ankyrin-B+/- cardiomyocytes results in disorganized distribution of B56 that can be rescued by exogenous expression of ankyrin-B. These new data implicate ankyrin-B as a critical targeting component for PP2A in heart and identify a new class of signaling proteins targeted by ankyrin polypeptides.
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