Casein kinase I associates with members of the centaurin-α family of phosphatidylinositol 3,4,5-trisphosphate-binding proteins

Mammalian casein kinases I (CKI) belong to a family of serine/threonine protein kinases involved in diverse cellular processes including cell cycle progression, membrane trafficking, circadian rhythms, and Wnt signaling. Here we show that CKI alpha co purifies with centaurin-alpha (1), in brain and that they interact in vitro and form a complex in cells. In addition, we show that the association is direct and occurs through the kinase domain of CKI within a loop comprising residues 217-233. These residues are well conserved in all members of the CKI: family, and we show that centaurin-alpha (1) associates in vitro with all mammalian CKI isoforms. To date, CKI alpha represents the first protein partner identified for centaurin-alpha (1). However, our data suggest that centaurin-alpha (1), is not a substrate for CKI alpha and has no effect on CKI alpha activity. Centaurin-alpha (1), has been identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein. Centaurin-alpha (1), contains a cysteine-rich domain that is shared by members of a newly identified family of ADP-ribosylation factor guanosine trisphosphatase-activating proteins. These proteins are involved in membrane trafficking and actin cytoskeleton rearrangement, thus supporting a role for CKI alpha in these biological events.