The interaction between casein kinase Iα and 14‐3‐3 is phosphorylation dependent

Abstract

We have previously shown that casein kinase (CK) Ialpha from mammalian brain phosphorylates 14-3-3 zeta and tau isoforms on residue 233. In the present study, we show that CKIalpha associates with 14-3-3 both in vitro and in vivo. The interaction between CKIalpha and 14-3-3 is dependent on CKIalpha phosphorylation, unlike centaurin-alpha1 (also known as ADAP1), which binds to unphosphorylated CKIalpha on the same region. CKIalpha 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 CKIalpha binding site was mutated and the interaction between CKIalpha and 14-3-3 was reduced. We subsequently identified a second phosphorylation-dependent 14-3-3 binding site within CKIalpha 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.