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

We have previously shown that casein kinase (CK) Iα from mammalian brain phosphorylates 14‐3‐3 ζ and τ isoforms on residue 233. In the present study, we show that CKIα associates with 14‐3‐3 both in vitro and in vivo. The interaction between CKIα and 14‐3‐3 is dependent on CKIα phosphorylation, unlike centaurin‐α1 (also known as ADAP1), which binds to unphosphorylated CKIα on the same region. CKIα preferentially interacts with mammalian η and γ 14‐3‐3 isoforms, and peptides that bind to the 14‐3‐3 binding pocket prevent this interaction. The region containing Ser218 in this CKIα binding site was mutated and the interaction between CKIα and 14‐3‐3 was reduced. We subsequently identified a second phosphorylation‐dependent 14‐3‐3 binding site within CKIα 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.

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