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Regulation of casein kinase I epsilon activity by Wnt signaling.

Publication ,  Journal Article
Swiatek, W; Tsai, I-C; Klimowski, L; Pepler, A; Barnette, J; Yost, HJ; Virshup, DM
Published in: J Biol Chem
March 26, 2004

The Wnt/beta-catenin signaling pathway is important in both development and cancer. Casein kinase Iepsilon (CKIepsilon) is a positive regulator of the canonical Wnt pathway. CKIepsilon itself can be regulated in vitro by inhibitory autophosphorylation, and recent data suggest that in vivo kinase activity can be regulated by extracellular stimuli. We show here that the phosphorylation state and kinase activity of CKIepsilon are directly regulated by Wnt signaling. Coexpression of XWnt-8 or addition of soluble Wnt-3a ligand led to a significant and rapid increase in the activity of endogenous CKIepsilon. The increase in CKIepsilon activity is the result of decreased inhibitory autophosphorylation because it is abolished by preincubation of immunoprecipitated kinase with ATP. Furthermore, mutation of CKIepsilon inhibitory autophosphorylation sites creates a kinase termed CKIepsilon(MM2) that is significantly more active than CKIepsilon and is not activated further upon Wnt stimulation. Autoinhibition of CKIepsilon is biologically relevant because CKIepsilon(MM2) is more effective than CKIepsilon at activating transcription from a Lef1-dependent promoter. Finally, CKIepsilon(MM2) expression in Xenopus embryos induces both axis duplication and additional developmental abnormalities. The data suggest that Wnt signaling activates CKIepsilon by causing transient dephosphorylation of critical inhibitory sites present in the carboxyl-terminal domain of the kinase. Activation of the Wnt pathway may therefore stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 26, 2004

Volume

279

Issue

13

Start / End Page

13011 / 13017

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Xenopus Proteins
  • Xenopus
  • Wnt Proteins
  • Transfection
  • Time Factors
  • Signal Transduction
  • Proto-Oncogene Proteins
  • Protein Kinases
  • Precipitin Tests
 

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Swiatek, W., Tsai, I.-C., Klimowski, L., Pepler, A., Barnette, J., Yost, H. J., & Virshup, D. M. (2004). Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem, 279(13), 13011–13017. https://doi.org/10.1074/jbc.M304682200
Swiatek, Wojciech, I-Chun Tsai, Laura Klimowski, Andrea Pepler, Janet Barnette, H Joseph Yost, and David M. Virshup. “Regulation of casein kinase I epsilon activity by Wnt signaling.J Biol Chem 279, no. 13 (March 26, 2004): 13011–17. https://doi.org/10.1074/jbc.M304682200.
Swiatek W, Tsai I-C, Klimowski L, Pepler A, Barnette J, Yost HJ, et al. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 2004 Mar 26;279(13):13011–7.
Swiatek, Wojciech, et al. “Regulation of casein kinase I epsilon activity by Wnt signaling.J Biol Chem, vol. 279, no. 13, Mar. 2004, pp. 13011–17. Pubmed, doi:10.1074/jbc.M304682200.
Swiatek W, Tsai I-C, Klimowski L, Pepler A, Barnette J, Yost HJ, Virshup DM. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 2004 Mar 26;279(13):13011–13017.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 26, 2004

Volume

279

Issue

13

Start / End Page

13011 / 13017

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Xenopus Proteins
  • Xenopus
  • Wnt Proteins
  • Transfection
  • Time Factors
  • Signal Transduction
  • Proto-Oncogene Proteins
  • Protein Kinases
  • Precipitin Tests