title: Regulation of sodium-calcium exchanger activity by creatine kinase.
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 [Ca(2+)](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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Yang
authors.forename: Lung-Sen
authors.initials: LS
authors.lastname: Kao
mesh_terms: D000818:Animals; D052281:Creatine Kinase, Mitochondrial Form / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D052281:Creatine Kinase, Mitochondrial Form