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Regulation of Sodium-Calcium Exchanger Activity by Creatine Kinase

  • Ya-Chi Yang
  • Lung-Sen KaoEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Sodium-calcium exchanger1 (NCX1) Creatine kinase Energy-compromised conditions NCX1 macromolecular complex 

Notes

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Institute of Biochemistry and Molecular BiologyNational Yang-Ming UniversityTaipeiRepublic of China
  2. 2.Department of Life Sciences and Institute of Genome SciencesNational Yang-Ming UniversityTaipeiRepublic of China

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