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Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex.

Publication ,  Journal Article
Gao, Z-H; Seeling, JM; Hill, V; Yochum, A; Virshup, DM
Published in: Proc Natl Acad Sci U S A
February 5, 2002

Wnt signaling plays a key role in cell proliferation and development. Recently, casein kinase I (CKI) and protein phosphatase 2A (PP2A) have emerged as positive and negative regulators of the Wnt pathway, respectively. However, it is not clear how these two enzymes with opposing functions regulate Wnt signaling. Here we show that both CKI delta and CKI epsilon interacted directly with Dvl-1, and that CKI phosphorylated multiple components of the Wnt-regulated beta-catenin degradation complex in vitro, including Dvl-1, adenomatous polyposis coli (APC), axin, and beta-catenin. Comparison of peptide maps from in vivo and in vitro phosphorylated beta-catenin and axin suggests that CKI phosphorylates these proteins in vivo as well. CKI abrogated beta-catenin degradation in Xenopus egg extracts. Notably, CKI decreased, whereas inhibition of CKI increased, the association of PP2A with the beta-catenin degradation complex in vitro. Additionally, inhibition of CKI in vivo stabilized the beta-catenin degradation complex, suggesting that CKI actively destabilizes the complex in vivo. The ability of CKI to induce secondary body axes in Xenopus embryos was reduced by the B56 regulatory subunit of PP2A, and kinase-dead CKI epsilon acted synergistically with B56 in inhibiting Wnt signaling. The data suggest that CKI phosphorylates and destabilizes the beta-catenin degradation complex, likely through the dissociation of PP2A, providing a mechanism by which CKI stabilizes beta-catenin and propagates the Wnt signal.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 5, 2002

Volume

99

Issue

3

Start / End Page

1182 / 1187

Location

United States

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Xenopus laevis
  • Xenopus Proteins
  • Wnt Proteins
  • Transfection
  • Transcription, Genetic
  • Trans-Activators
  • Saccharomyces cerevisiae
  • Repressor Proteins
 

Citation

APA
Chicago
ICMJE
MLA
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Gao, Z.-H., Seeling, J. M., Hill, V., Yochum, A., & Virshup, D. M. (2002). Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci U S A, 99(3), 1182–1187. https://doi.org/10.1073/pnas.032468199
Gao, Zhong-Hua, Joni M. Seeling, Virginia Hill, April Yochum, and David M. Virshup. “Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex.Proc Natl Acad Sci U S A 99, no. 3 (February 5, 2002): 1182–87. https://doi.org/10.1073/pnas.032468199.
Gao Z-H, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1182–7.
Gao, Zhong-Hua, et al. “Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex.Proc Natl Acad Sci U S A, vol. 99, no. 3, Feb. 2002, pp. 1182–87. Pubmed, doi:10.1073/pnas.032468199.
Gao Z-H, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1182–1187.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 5, 2002

Volume

99

Issue

3

Start / End Page

1182 / 1187

Location

United States

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Xenopus laevis
  • Xenopus Proteins
  • Wnt Proteins
  • Transfection
  • Transcription, Genetic
  • Trans-Activators
  • Saccharomyces cerevisiae
  • Repressor Proteins