ZFIN ID: ZDB-PUB-030826-11
A noncanonical sequence phosphorylated by casein kinase 1 in {beta}-catenin may play a role in casein kinase 1 targeting of important signaling proteins
Marin, O., Bustos, V.H., Cesaro, L., Meggio, F., Pagano, M.A., Antonelli, M., Allende, C.C., Pinna, L.A., and Allende, J.E.
Date: 2003
Source: Proceedings of the National Academy of Sciences of the United States of America   100(18): 10193-200 (Journal)
Registered Authors: Allende, Jorge E., Antonelli, Marcelo
Keywords: none
MeSH Terms:
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Casein Kinases
  • Cytoskeletal Proteins/chemistry*
  • Cytoskeletal Proteins/metabolism
  • DNA-Binding Proteins/chemistry
  • Glycogen Synthase Kinase 3/physiology
  • Models, Molecular
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phosphorylation
  • Protein Kinases/physiology*
  • Rats
  • Signal Transduction/physiology*
  • Structure-Activity Relationship
  • Trans-Activators/chemistry*
  • Trans-Activators/metabolism
  • Transcription Factors/chemistry
  • beta Catenin
PubMed: 12925738 Full text @ Proc. Natl. Acad. Sci. USA
This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on May 1, 2001. 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 CK1alpha and CK1alphaL 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.