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Regulation of Sodium-Calcium Exchanger Activity by Creatine Kinase

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Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 961))

Abstract

It has been shown that in rat heart NCX1 exists in a macromolecular ­complex including PKA, PKA-anchoring protein, PKC, and phosphatases PP1 and PP2A. In addition, several lines of evidence suggest that the interactions of the exchanger with other molecules are closely associated with its function in regulation of [Ca2+]i. NCX contains a large intracellular loop (NCXIL) that is responsible for regulating NCX activity. We used the yeast two-hybrid method to screen a human heart cDNA library and found that the C-terminal region of sarcomeric mitochondrial creatine kinase (sMiCK) interacted with NCX1IL. Among the four creatine kinase (CK) isozymes, both sMiCK and the muscle-type cytosolic creatine kinase (CKM) co-immunoprecipitated with NCX1. Both sMiCK and CKM were able to produce a recovery in the decreased NCX1 activity that was lost under energy-compromised conditions. This regulation is mediated through a putative PKC phosphorylation site of sMiCK and CKM. The catalytic activity of sMiCK and CKM is not required for their regulation of NCX1 activity. Our results suggest a novel mechanism for the regulation of NCX1 activity and a novel role for CK.

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Acknowledgments

This research was originally published in the Journal of Biological Chemistry; Yang, Y.-C., Fann, M.-J., Chang, W.-H., Tai, L.-H., Jiang, J.-H., and Kao, L.-S. (2010) Regulation of sodium-calcium exchanger activity by creatine kinase under energy-compromised conditions. J. Biol. Chem. Vol. 285, 28275–28285 © the American Society for Biochemistry and Molecular Biology.

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, 112, Republic of China

    Ya-Chi Yang

  2. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, 112, Republic of China

    Lung-Sen Kao Ph.D.

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  1. Ya-Chi Yang
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Correspondence to Lung-Sen Kao Ph.D. .

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  1. Dipto. Neuroscienze e di, Università di Napoli Fac. Medicina e Chirurgia, Napoli, Italy

    Lucio Annunziato

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Yang, YC., Kao, LS. (2013). Regulation of Sodium-Calcium Exchanger Activity by Creatine Kinase. In: Annunziato, L. (eds) Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications. Advances in Experimental Medicine and Biology, vol 961. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4756-6_14

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