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First published online 22 December 2004
doi: 10.1242/jcs.01601

Journal of Cell Science 118, 313-322 (2005)
Published by The Company of Biologists 2005
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Research Article

Both ERK and Wnt/ß-catenin pathways are involved in Wnt3a-induced proliferation

Mi-Sun Yun1,*, Sung-Eun Kim1,*, Soung Hoo Jeon1, Jung-Soo Lee1 and Kang-Yell Choi1,2,{ddagger}

1 Department of Biotechnology, Yonsei University, Seoul 120-752, Korea
2 Protein Network Research Center, Yonsei University, Seoul 120-752, Korea

{ddagger} Author for correspondence (e-mail: kychoi{at}yonsei.ac.kr)

Accepted 21 October 2004

The Wnt family of proteins regulates development and cell growth. We identified Wnt3a-based regulatory mechanisms for cell proliferation in NIH3T3 fibroblast cells. The degree of Wnt3a-induced proliferation was reduced by ß-catenin small interfering RNA (siRNA) and extracellular signal-regulated kinase (ERK) siRNA, indicating that both the ERK and Wnt/ß-catenin pathways are involved in Wnt3a-induced proliferation. Wnt3a immediately and transiently activated the Raf-1-MEK-ERK cascade in a manner distinct from that of the ß-catenin increase seen in cells treated with Wnt3a. Wnt3a-induced ERK activation was maintained even though basal ERK activities were reduced by ß-catenin siRNA, indicating that Wnt3a may activate the ERK pathway independently of ß-catenin. The ERK pathway was however, activated by ß-catenin transfection, which was abolished by co-transfection with dominant-negative Tcf-4. Therefore, ERK pathway activation by Wnt signaling could occur at multiple levels, including ß-catenin-independent direct signaling resulting from a Wnt3a and ß-catenin/Tcf-4-dependent post gene transcriptional event. Wnt3a stimulated the G1 to S phase cell cycle progression. This stimulation was reduced by the ERK pathway inhibitor, indicating that Wnt3a promotes proliferation by stimulating the ERK pathway. Wnt3a therefore stimulates the proliferation of fibroblast cells, at least in part, via activation of the ERK and Wnt/ß-catenin pathways.

Key words: Wnt3a, Wnt signaling, ß-catenin, Proliferation, ERK pathway


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