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Molecular Regulation of Phospholamban Function and Gene Expression a
Author(s) -
TADA MICHIHIKO,
YABUKI MASANORI,
TOYOFUKU TOSHIHIKO
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08261.x
Subject(s) - phospholamban , endoplasmic reticulum , binding site , mutagenesis , luciferase , chemistry , atpase , microbiology and biotechnology , gene expression , gene , biology , biochemistry , transfection , mutation , enzyme
Ca‐ATPase regulates intracellular Ca levels by pumping Ca into sarcoplasmic reticulum. Phospholamban (PLN) functions as an inhibitory cofactor for cardiac Ca‐ATPase (SERCA2). To define the molecular mode of interaction between two proteins, interaction sites have been identified. Studies using photoactivated cross‐linker and chimeric Ca‐ATPase between SERCA2 and nonmuscle Ca‐ATPase (SERCA3) indicated that potential binding residues are located just downstream of the active ATPase site (Asp351) of SERCA2. Site‐directed mutagenesis study of this region showed that six residues, Lys‐Asp‐Asp‐Lys‐Pro‐Val402, of SERCA2 are functionally important for the interaction. Further, mutagenesis study of PLN showed that the cytoplasmic region of PLN contains a potential binding site with SERCA2. The unique expression of PLN in cardiac cells has been analyzed by the transcriptional level of its gene using luciferase activity and Gel shift assays. CCAAT‐box in the 5′‐upstream region was found to be essential for its expression by associating with Y‐box binding transcriptional factors.