FAK overexpression upregulates cyclin D3 and enhances cell proliferation via the PKC and PI3-kinase-Akt pathways

Daisuke Yamamoto, Yoshiko Sonoda, Maki Hasegawa, Megumi Tago, Eriko Yokota, Tadashi Kasahara

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

We previously demonstrated that FAK-transfected HL-60 (HL-60/FAK) cells exhibit anti-apoptotic capacity. Here, we report that HL-60/FAK cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. This observation prompted us to investigate the mechanism of how HL-60/FAK cells augment cell proliferation. Since a protein kinase C (PKC) inhibitor, chelerythrine, or a PI3-kinase inhibitor, LY294002, suppressed cell proliferation effectively, both PKC and PI-3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, particularly PKCα, β and η isoforms were activated and directly associated with FAK in HL-60/FAK cells. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity.

Original languageEnglish
Pages (from-to)575-583
Number of pages9
JournalCellular Signalling
Volume15
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1

Fingerprint

Cyclin D3
HL-60 Cells
Phosphatidylinositol 3-Kinases
Up-Regulation
Cell Proliferation
Protein Kinase C
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclins
Protein C Inhibitor
Protein Kinase Inhibitors
protein kinase C kinase
Protein Isoforms

Keywords

  • Akt
  • Cell proliferation
  • Cyclin D3
  • Focal adhesion kinase
  • Phosphatidylinositol 3-kinase
  • PKC

ASJC Scopus subject areas

  • Cell Biology

Cite this

FAK overexpression upregulates cyclin D3 and enhances cell proliferation via the PKC and PI3-kinase-Akt pathways. / Yamamoto, Daisuke; Sonoda, Yoshiko; Hasegawa, Maki; Tago, Megumi; Yokota, Eriko; Kasahara, Tadashi.

In: Cellular Signalling, Vol. 15, No. 6, 01.06.2003, p. 575-583.

Research output: Contribution to journalArticle

Yamamoto, Daisuke ; Sonoda, Yoshiko ; Hasegawa, Maki ; Tago, Megumi ; Yokota, Eriko ; Kasahara, Tadashi. / FAK overexpression upregulates cyclin D3 and enhances cell proliferation via the PKC and PI3-kinase-Akt pathways. In: Cellular Signalling. 2003 ; Vol. 15, No. 6. pp. 575-583.
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