SRF-dependent gene expression is required for P13-kinase-regulated cell proliferation

Steve Poser, Soren Impey, Kien Trinh, Zhengui Xia, Daniel R. Storm

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Recent evidence indicates that phosphatidylinositol 3-kinase (PI3K) is a central regulator of mitosis, apoptosis and oncogenesis. Nevertheless, the mechanisms by which PI3K regulates proliferation are not well characterized. Mitogens stimulate entry into the cell cycle by inducing the expression of immediate early genes (IEGs) that in turn trigger the expression of G1 cyclins. Here we describe a novel PI3K-regulated transcriptional cascade that is critical for mitogen regulation of the IEG, c-fos. We show that PI3K activates gene expression by transactivating SRF-dependent transcription independently of the previously described Rho and ETS TCF pathways. PI3K-stimulated cell cycle progression requires transactivation of SRF and expression of dominant-negative PI3K blocks mitogen-stimulated cell cycle progression. Furthermore, dominant-interfering SRF mutants attenuate mitogen-stimulated cell cycle progression, but are without effect on MEK-stimulated cell cycle entry. Moreover, expression of constitutively active SRF is sufficient for cell cycle entry. Thus, we delineate a novel SRF-dependent mitogenic cascade that is critical for PI3K- and growth factor-mediated cell cycle progression.

Original languageEnglish (US)
Pages (from-to)4955-4966
Number of pages12
JournalEMBO Journal
Volume19
Issue number18
StatePublished - Sep 15 2000

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Keywords

  • Cell cycle
  • PI3-kinase
  • Serum response element
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Poser, S., Impey, S., Trinh, K., Xia, Z., & Storm, D. R. (2000). SRF-dependent gene expression is required for P13-kinase-regulated cell proliferation. EMBO Journal, 19(18), 4955-4966.