Modulation of the ABCA1 transporter activity by protein kinase CK2

摘要

We identified putative protein kinase CK2 phosphorylation sites in the cytoplasmic Rl and R2 domains, downstream of nucleotide binding dornains (NBD) of the ABCA1 transporter, and tested their functional significance.In vitro, the recombinant ABCA1 NBD1 +R1 domain, and not the NBD2 + R2 domain, was phosphoiylated by CK2.We identified T1242, T1243 and S1255 as the phosphorylated residues in the Rl domain.In HEK-293 cells, ABCA1 flippase activity, apolipopioteins AI and All binding to the cell, and cellular phospholipid and cholesterol efflux were enhanced by mutations preventing CK2 phosphorylation of the threonine residues Mutants mimicking threonine phosphorylation had activities close to that of WT ABCA1.Our data therefore suggest that protein kinase CK2 might regulate the transport activity of ABCA1 in vivo.