Cited by 121Wnt/β-catenin signaling in development and cancerCongenital heart defects researchPluripotent Stem Cells Research

Phosphatidylinositol 3-Kinase–Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling

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Naito, Atsuhiko T., Akazawa, Hiroshi, Takano, Hiroyuki, Minamino, Tohru, Nagai, Toshio, Aburatani, Hiroyuki, Komuro, Issei·2005·Circulation Research

Abstract

We have recently reported that activation of phosphatidylinositol 3-kinase (PI3K) plays a critical role in the early stage of cardiomyocyte differentiation of P19CL6 cells. We here examined molecular mechanisms of how PI3K is involved in cardiomyocyte differentiation. DNA chip analysis revealed that expression levels of Wnt-3a were markedly increased and that the Wnt/β-catenin pathway was activated temporally during the early stage of cardiomyocyte differentiation of P19CL6 cells. Activation of the Wnt/β-catenin pathway during this period was required and sufficient for cardiomyocyte differentiation of P19CL6 cells. Inhibition of the PI3K/Akt pathway suppressed the Wnt/β-catenin pathway by activation of glycogen synthase kinase-3β (GSK-3β) and degradation of β-catenin. Suppression of cardiomyocyte differentiation by inhibiting the PI3K/Akt pathway was rescued by forced expression of a nonphosphorylated, constitutively active form of β-catenin. These results suggest that the PI3K pathway regulates cardiomyocyte differentiation through suppressing the GSK-3β activity and maintaining the Wnt/β-catenin activity.

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  • GSK-3β controls cell survival through regulation of β-catenin, and inhibition of Akt suppresses the Wnt pathway by activation of GSK-3β and degradation of β-catenin.

    “At the same time, GSK-3β also controls cell survival through regulation of β-catenin, 1 of the key molecules in Wnt signaling (11), and inhibition of Akt suppresses the Wnt pathway by activation of GSK-3β and degradation of ß-catenin (51).”

    From Anabolic effect of plant brassinosteroid (2011) · cites this paper as [51]

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Authors
Naito, A. T., Akazawa, H., Takano, H., Minamino, T., Nagai, T., Aburatani, H., & Komuro, I.
Affiliations
Chiba University (JP)
Venue
Circulation Research
Published
2005-07-22
Volume
97
Issue
2
Pages
144-151
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2153811819
Cited by
121
References
40
Citations by year
2026: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 9
FWCI
4.02
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • Japan Health Sciences Foundation
  • Japan Heart Foundation
  • Pfizer Japan
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
phosphatidylinositol 3-kinase, Akt signaling, cardiomyocyte differentiation, cardiomyogenesis, Wnt/β-catenin signaling, Wnt3a, glycogen synthase kinase-3β, β-catenin degradation, P19CL6 cells
MeSH terms
Glycogen Synthase Kinase 3 beta, Animals, Cell Differentiation, Cells, Cultured, Cytoskeletal Proteins, Dimethyl Sulfoxide, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Myocytes, Cardiac, Intercellular Signaling Peptides and Proteins, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Wnt Proteins, beta Catenin, Mice

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