We have previously shown that casein kinase (CK) I alpha from mammalian brain phosphorylates 14-3-3 zeta and tau isoforms on residue 233. In the present study, we show that CKI alpha associates with 14-3-3 both in vitro and in vivo. The interaction between CKI alpha and 14-3-3 is dependent on CKI alpha phosphorylation, unlike centaurin-alpha 1 (also known as ADAP1), which binds to unphosphorylated CKI alpha on the same region. CKI alpha preferentially interacts with mammalian eta and gamma 14-3-3 isoforms, and peptides that bind to the 14-3-3 binding pocket prevent this interaction. The region containing Ser218 in this CKI alpha binding site was mutated and the interaction between CKI alpha and 14-3-3 was reduced. We subsequently identified a second phosphorylation-dependent 14-3-3 binding site within CKI alpha containing Ser242 that may be the principal site of interaction. We also show that both fission and budding yeast CKI kinase homologues phosphorylate mammalian and budding yeast (BMH1 and BMH2) 14-3-3 at the equivalent site.
- centaurin alpha