Protein kinase casein kinase 1 (CK1) phosphorylates Ser-45 of beta-catenin, 
"priming" the subsequent phosphorylation by glycogen synthase-3 of residues 41, 
37, and 33. This concerted phosphorylation of beta-catenin signals its 
degradation and prevents its function in triggering cell division. The sequence 
around Ser-45 does not conform to the canonical consensus for CK1 substrates, 
which prescribes either phosphoamino acids or acidic residues in position n-3 
from the target serine. However, the beta-catenin sequence downstream from 
Ser-45 is very similar to a sequence recognized by CK1 in nuclear factor for 
activated T cells 4. The common features include an SLS motif followed two to 
five residues downstream by a cluster of acidic residues. Synthetic peptides 
reproducing residues 38-65 of beta-catenin were assayed with purified rat liver 
CK1 or recombinant CK1 alpha and CK1 alpha L from zebrafish. The results 
demonstrate that SLS and acidic cluster motifs are crucial for CK1 recognition. 
Pro-44 and Pro-52 are also important for efficient phosphorylation. Similar 
results were obtained with the different isoforms of CK1. Phosphorylation of 
mutants of full-length recombinant beta-catenin from zebrafish confirmed the 
importance of the SLS and acidic cluster motifs. A search for proteins with 
similar motifs yielded, among other proteins, adenomatous polyposis coli, 
previously found to be phosphorylated by CK1. There is a strong correlation of 
beta-catenin mutations found in thyroid tumors with the motifs recognized by CK1 
in this protein.