| To study the possible regulation of the ABCA 1 transporter by CK 2 , we expressed the recombinant cytoplasmic domains of ABCA 1 , NBD1+R1 and NBD2+R2 . ^^^ We demonstrated that in vitro ABCA 1 NBD1+R1 , and not NBD2+R2 , is phosphorylated by CK 2 , and we identified Thr 1242 , Thr 1243 , and Ser 1255 as the phosphorylated residues in the R 1 domain by mass spectrometry . ^^^ The ABCA 1 flippase activity , apolipoprotein AI and AII binding , and cellular phospholipid and cholesterol efflux were enhanced by mutations preventing CK 2 phosphorylation of the threonine and serine residues . ^^^ This was confirmed by the effect of specific protein kinase CK 2 inhibitors upon the activity of wild type and mutant ABCA 1 in transfected Hek 293 Tet Off cells . ^^^ Our data , therefore , suggest that besides protein kinase A and C , protein kinase CK 2 might play an important role in vivo in regulating the function and transport activity of ABCA 1 and possibly of other members of the ABCA subfamily . . ^^^ |