Both ERK and Wnt/beta-catenin pathways are involved in Wnt3a-induced proliferation.
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 beta-catenin small interfering RNA (siRNA) and extracellular signal-regulated kinase (ERK) siRNA, indicating that both the ERK and Wnt/beta-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 beta-catenin increase seen in cells treated with Wnt3a. Wnt3a-induced ERK activation was maintained even though basal ERK activities were reduced by beta-catenin siRNA, indicating that Wnt3a may activate the ERK pathway independently of beta-catenin. The ERK pathway was however, activated by beta-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 beta-catenin-independent direct signaling resulting from a Wnt3a and beta-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/beta-catenin pathways.
Yun
Mi-Sun
MS
Department of Biotechnology, Yonsei University, Seoul 120-752, Korea.
Kim
Sung-Eun
SE
Jeon
Soung Hoo
SH
Lee
Jung-Soo
JS
Choi
Kang-Yell
KY
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D048490:raf Kinases / Q000187:drug effects / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases