The sarco-endoplasmic reticulum calcium ATPase 2a (SERCA2a) is critical for sequestering cytosolic calcium into the sarco-endoplasmic reticulum (SR) and regulating cardiac muscle relaxation. Protein-protein interactions indicated that it exists in complex with Ca2+/ calmodulin-dependent protein kinase II (CaMKII) and its anchoring protein αKAP. Confocal imaging of isolated cardiomyocytes revealed the colocalization of CAMKII and αKAP with SERCA2a at the SR. Deletion analysis indicated that SERCA2a and CaMKII bind to different regions in the association domain of αKAP but not with each other. Although deletion of the putative N-terminal hydrophobic amino acid stretch inαKAP prevented its membrane targeting, it did not influence binding to SERCA2a or CaMKII. Both CaMKIIδC and the novel CaMKIIβ4 isoforms were found to exist in complex with αKAP and SERCA2a at the SR and were able to phosphorylate Thr-17 on phospholamban (PLN), an accessory subunit and known regulator of SERCA2a activity. Interestingly, the presence of αKAP was also found to significantly modulate the Ca2+/ calmodulin-dependent phosphorylation of Thr-17 on PLN. These data demonstrate that αKAP exhibits a novel interaction with SERCA2a and may serve to spatially position CaMKII isoforms at the SR and to uniquely modulate the phosphorylation of PLN. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
CITATION STYLE
Singh, P., Salih, M., & Tuana, B. S. (2009). α-kinase anchoring protein αKAP interacts with SERCA2A to spatially position Ca2+/calmodulin-dependent protein kinase II and modulate phospholamban phosphorylation. Journal of Biological Chemistry, 284(41), 28212–28221. https://doi.org/10.1074/jbc.M109.044990
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