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Alternative splicing generates a CaM kinase IIβ isoform in myocardium that targets the sarcoplasmic reticulum through a putative αKAP and regulates GAPDH

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Abstract

We report the isolation of a full length cDNA from cardiac muscle that encodes a ∼73 kDa calcium/calmodulin (CaM) dependent kinase IIβ isoform (CaMKIIβC) that was generated by alternative splicing of the CaMKIIβ gene. Antipeptide antibodies raised to specific regions of the kinase identified a 73 kDa kinase polypeptide in cardiac SR. Anti-alpha kinase anchoring protein (αKAP) antibodies identified a 25 kDa polypeptide in cardiac SR and RT-PCR followed by sequence analysis confirmed the presence of a full length αKAP encoding transcript in myocardium. Protein interaction assays revealed that the 73 kDa CaMKIIβC binds GAPDH to modulate the production of NADH in a Ca2+/CaM dependent reaction. The presence of a CaMKIIβ isoform that can target the SR presumably via its membrane anchor αKAP defines a previously unrecognized Ca2+/CaM regulatory system in myocardium. (Mol Cell Biochem 270: 215–221, 2005)

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Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, Canada, K1H 8M5

    Puneet Singh, John J. Leddy, George J. Chatzis, Maysoon Salih & Balwant S. Tuana

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  1. Puneet Singh
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  2. John J. Leddy
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  3. George J. Chatzis
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  4. Maysoon Salih
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  5. Balwant S. Tuana
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Correspondence to Balwant S. Tuana.

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Singh, P., Leddy, J.J., Chatzis, G.J. et al. Alternative splicing generates a CaM kinase IIβ isoform in myocardium that targets the sarcoplasmic reticulum through a putative αKAP and regulates GAPDH. Mol Cell Biochem 270, 215–221 (2005). https://doi.org/10.1007/s11010-005-5234-y

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  • DOI: https://doi.org/10.1007/s11010-005-5234-y

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