Molecular basis for PP2A regulatory subunit B56alpha targeting in cardiomyocytes
| Autor: | Shane R. Cunha, Malkanthi Mudannayake, Peter J. Mohler, Terry B. Rogers, Naina Bhasin, Marisa S. Gigena |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Ankyrins
Phosphoric monoester hydrolases Physiology Protein subunit Phosphatase Biology Substrate Specificity Rats Sprague-Dawley Mice Drug Delivery Systems Physiology (medical) ANK2 Phosphoprotein Phosphatases Animals Myocytes Cardiac Protein Phosphatase 2 Cytoskeleton Cells Cultured chemistry.chemical_classification Mice Knockout Binding Sites Protein phosphatase 2 Phosphoric Monoester Hydrolases Cell biology Rats Mice Inbred C57BL Enzyme chemistry Biochemistry Cardiology and Cardiovascular Medicine Function (biology) Protein Binding Subcellular Fractions |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 293(1) |
| ISSN: | 0363-6135 |
| Popis: | Protein phosphatase 2A (PP2A) is a multifunctional protein phosphatase with critical roles in excitable cell signaling. In the heart, PP2A function is linked with modulation of β-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. Although 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 B56α is an in vivo binding partner for ankyrin-B, an adapter protein required for normal subcellular localization of the Na/Ca exchanger, Na/K ATPase, and inositol 1,4,5-trisphosphate receptor. Ankyrin-B and B56α are colocalized and coimmunoprecipitate in primary cardiomyocytes. Using multiple strategies, we identified the structural requirements on B56α for ankyrin-B association as a 13 residue motif in the B56α COOH 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 B56α 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|