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

Mammalian casein kinases I (CKI) belong to a family of serine/threonine pro tein kinases involved in diverse cellular processes including cell cycle pr ogression, 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 sh ow that the association is direct and occurs through the kinase domain of C KI within a loop comprising residues 217-233. These residues are well conse rved 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 r epresents the first protein partner identified for centaurin-alpha (1). How ever, 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 be en identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein . Centaurin-alpha (1), contains a cysteine-rich domain that is shared by me mbers of a newly identified family of ADP-ribosylation factor guanosine tri sphosphatase-activating proteins. These proteins are involved in membrane t rafficking and actin cytoskeleton rearrangement, thus supporting a role for CKI alpha in these biological events.