Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways

Kosuke Torii, Koji Nishizawa, Aya Kawasaki, Yuki Yamashita, Masanori Katada, Minoru Ito, Ikuo Nishimoto, Kenzo Terashita, Sadakazu Aiso, Masaaki Matsuoka

Research output: Contribution to journalArticle

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Abstract

Wnts are secreted glycoproteins that control diverse biological processes, such as proliferation, differentiation, and apoptosis. We here found that Wnt5a inhibited apoptosis induced by serum deprivation in primary-cultured human dermal fibroblasts. Anti-apoptotic activity of Wnt5a was not inhibited by a dickkopf-1 (DKK), which blocks the canonical Wnt pathway. On the other hand, loss of function of protein kinase A (PKA), induced by treatment with PKA inhibitors, siRNA-mediated knocking down of endogenous PKA catalytic subunits, or enforced expression of dominant-negative PKA inhibited the Wnt5a anti-apoptotic activity, indicating the involvement of PKA in the Wnt5a anti-apoptotic activity. In agreement, phosphorylation levels of a cAMP response element binding protein (CREB), a representative downstream effector of PKA, the activation of which is known to lead to the pro-survival effects, was elevated by Wnt5a. In addition, Wnt5a increased the nuclear β-catenin level and treatment with imatinib or ionomycin, either of which blocks the β-catenin pathway, reduced the anti-apoptotic activity of Wnt5a, together suggesting the simultaneous involvement of the β-catenin-mediated pathway in the Wnt5a anti-apoptotic activity. Based on another finding indicating that Wnt5a upregulated PKA-mediated phosphorylation of glycogen synthase kinase-3β (GSK-3β) at serine 9 that caused inactivation of GSK-3β and subsequently resulted in activation of the β-catenin pathway, we have speculated that the Wnt5a anti-apoptotic activity may be partially mediated by PKA-mediated phosphorylation of GSK-3β and subsequent activation of the β-catenin pathway.

Original languageEnglish
Pages (from-to)1256-1266
Number of pages11
JournalCellular Signalling
Volume20
Issue number7
DOIs
Publication statusPublished - 2008 Jul

Fingerprint

Cyclic AMP-Dependent Protein Kinases
Catenins
Fibroblasts
Skin
Glycogen Synthase Kinase 3
Phosphorylation
Apoptosis
Biological Phenomena
Cyclic AMP Response Element-Binding Protein
Ionomycin
Wnt Signaling Pathway
Protein Kinase Inhibitors
Serine
Small Interfering RNA
Catalytic Domain
Glycoproteins
Survival
Serum

Keywords

  • β-catenin
  • Apoptosis
  • PKA
  • Wnt5a

ASJC Scopus subject areas

  • Cell Biology

Cite this

Torii, K., Nishizawa, K., Kawasaki, A., Yamashita, Y., Katada, M., Ito, M., ... Matsuoka, M. (2008). Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways. Cellular Signalling, 20(7), 1256-1266. https://doi.org/10.1016/j.cellsig.2008.02.013

Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways. / Torii, Kosuke; Nishizawa, Koji; Kawasaki, Aya; Yamashita, Yuki; Katada, Masanori; Ito, Minoru; Nishimoto, Ikuo; Terashita, Kenzo; Aiso, Sadakazu; Matsuoka, Masaaki.

In: Cellular Signalling, Vol. 20, No. 7, 07.2008, p. 1256-1266.

Research output: Contribution to journalArticle

Torii, K, Nishizawa, K, Kawasaki, A, Yamashita, Y, Katada, M, Ito, M, Nishimoto, I, Terashita, K, Aiso, S & Matsuoka, M 2008, 'Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways', Cellular Signalling, vol. 20, no. 7, pp. 1256-1266. https://doi.org/10.1016/j.cellsig.2008.02.013
Torii, Kosuke ; Nishizawa, Koji ; Kawasaki, Aya ; Yamashita, Yuki ; Katada, Masanori ; Ito, Minoru ; Nishimoto, Ikuo ; Terashita, Kenzo ; Aiso, Sadakazu ; Matsuoka, Masaaki. / Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways. In: Cellular Signalling. 2008 ; Vol. 20, No. 7. pp. 1256-1266.
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