Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity

Dexing Fang, David Hawke, Yanhua Zheng, Yan Xia, Jill Meisenhelder, Heinz Nika, Gordon Mills, Ryuji Kobayashi, Tony Hunter, Zhimin Lu

Research output: Contribution to journalArticle

510 Citations (Scopus)

Abstract

Increased transcriptional activity of β-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.

Original languageEnglish (US)
Pages (from-to)11221-11229
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number15
DOIs
StatePublished - Apr 13 2007
Externally publishedYes

Fingerprint

Catenins
Phosphorylation
Tumors
Neoplasms
Epidermal Growth Factor Receptor
Cytosol
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fang, D., Hawke, D., Zheng, Y., Xia, Y., Meisenhelder, J., Nika, H., ... Lu, Z. (2007). Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. Journal of Biological Chemistry, 282(15), 11221-11229. https://doi.org/10.1074/jbc.M611871200

Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. / Fang, Dexing; Hawke, David; Zheng, Yanhua; Xia, Yan; Meisenhelder, Jill; Nika, Heinz; Mills, Gordon; Kobayashi, Ryuji; Hunter, Tony; Lu, Zhimin.

In: Journal of Biological Chemistry, Vol. 282, No. 15, 13.04.2007, p. 11221-11229.

Research output: Contribution to journalArticle

Fang, D, Hawke, D, Zheng, Y, Xia, Y, Meisenhelder, J, Nika, H, Mills, G, Kobayashi, R, Hunter, T & Lu, Z 2007, 'Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity', Journal of Biological Chemistry, vol. 282, no. 15, pp. 11221-11229. https://doi.org/10.1074/jbc.M611871200
Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H et al. Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. Journal of Biological Chemistry. 2007 Apr 13;282(15):11221-11229. https://doi.org/10.1074/jbc.M611871200
Fang, Dexing ; Hawke, David ; Zheng, Yanhua ; Xia, Yan ; Meisenhelder, Jill ; Nika, Heinz ; Mills, Gordon ; Kobayashi, Ryuji ; Hunter, Tony ; Lu, Zhimin. / Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 15. pp. 11221-11229.
@article{dbcbd31a0d964b8a8f4b61aa43a3420f,
title = "Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity",
abstract = "Increased transcriptional activity of β-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.",
author = "Dexing Fang and David Hawke and Yanhua Zheng and Yan Xia and Jill Meisenhelder and Heinz Nika and Gordon Mills and Ryuji Kobayashi and Tony Hunter and Zhimin Lu",
year = "2007",
month = "4",
day = "13",
doi = "10.1074/jbc.M611871200",
language = "English (US)",
volume = "282",
pages = "11221--11229",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "15",

}

TY - JOUR

T1 - Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity

AU - Fang, Dexing

AU - Hawke, David

AU - Zheng, Yanhua

AU - Xia, Yan

AU - Meisenhelder, Jill

AU - Nika, Heinz

AU - Mills, Gordon

AU - Kobayashi, Ryuji

AU - Hunter, Tony

AU - Lu, Zhimin

PY - 2007/4/13

Y1 - 2007/4/13

N2 - Increased transcriptional activity of β-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.

AB - Increased transcriptional activity of β-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.

UR - http://www.scopus.com/inward/record.url?scp=34249661591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249661591&partnerID=8YFLogxK

U2 - 10.1074/jbc.M611871200

DO - 10.1074/jbc.M611871200

M3 - Article

C2 - 17287208

AN - SCOPUS:34249661591

VL - 282

SP - 11221

EP - 11229

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 15

ER -