The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca2+ pathway to antagonize Wnt/β-catenin signaling

Tohru Ishitani, Satoshi Kishida, Junko Hyodo-Miura, Naoto Ueno, Jun Yasuda, Marian Waterman, Hiroshi Shibuya, Randall T. Moon, Jun Ninomiya-Tsuji, Kunihiro Matsumoto

Research output: Contribution to journalArticle

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Abstract

Wnt signaling controls a variety of developmental processes. The canonical Wnt/β-catenin pathway functions to stabilize β-catenin, and the noncanonical Wnt/Ca2+ pathway activates Ca2+/calmodulin-dependent protein kinase II (CaMKII). In addition, the Wnt/Ca2+ pathway activated by Wnt-5a antagonizes the Wnt/β-catenin pathway via an unknown mechanism. The mitogen-activated protein kinase (MAPK) pathway composed of TAK1 MAPK kinase kinase and NLK MAPK also negatively regulates the canonical Wnt/β-catenin signaling pathway. Here we show that activation of CaMKII induces stimulation of the TAK1-NLK pathway. Overexpression of Wnt-5a in HEK293 cells activates NLK through TAK1. Furthermore, by using a chimeric receptor (β2AR-Rfz-2) containing the ligand-binding and transmembrane segments from the β2-adrenergic receptor (β2AR) and the cytoplasmic domains from rat Frizzled-2 (Rfz-2), stimulation with the β-adrenergic agonist isoproterenol activates activities of endogenous CaMKII, TAK1, and NLK and inhibits β-catenin-induced transcriptional activation. These results suggest that the TAK1-NLK MAPK cascade is activated by the noncanonical Wnt-5a/Ca2+ pathway and antagonizes canonical Wnt/β-catenin signaling.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalMolecular and cellular biology
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2003

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Catenins
Wnt Signaling Pathway
Mitogen-Activated Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Adrenergic Receptors
MAP Kinase Kinase Kinases
Adrenergic Agonists
HEK293 Cells
Isoproterenol
Transcriptional Activation
Ligands

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca2+ pathway to antagonize Wnt/β-catenin signaling. / Ishitani, Tohru; Kishida, Satoshi; Hyodo-Miura, Junko; Ueno, Naoto; Yasuda, Jun; Waterman, Marian; Shibuya, Hiroshi; Moon, Randall T.; Ninomiya-Tsuji, Jun; Matsumoto, Kunihiro.

In: Molecular and cellular biology, Vol. 23, No. 1, 01.01.2003, p. 131-139.

Research output: Contribution to journalArticle

Ishitani, T, Kishida, S, Hyodo-Miura, J, Ueno, N, Yasuda, J, Waterman, M, Shibuya, H, Moon, RT, Ninomiya-Tsuji, J & Matsumoto, K 2003, 'The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca2+ pathway to antagonize Wnt/β-catenin signaling', Molecular and cellular biology, vol. 23, no. 1, pp. 131-139. https://doi.org/10.1128/MCB.23.1.131-139.2003
Ishitani, Tohru ; Kishida, Satoshi ; Hyodo-Miura, Junko ; Ueno, Naoto ; Yasuda, Jun ; Waterman, Marian ; Shibuya, Hiroshi ; Moon, Randall T. ; Ninomiya-Tsuji, Jun ; Matsumoto, Kunihiro. / The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca2+ pathway to antagonize Wnt/β-catenin signaling. In: Molecular and cellular biology. 2003 ; Vol. 23, No. 1. pp. 131-139.
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