B-Raf and insulin synergistically prevent apoptosis and induce cell cycle progression in hematopoietic cells

John G. Shelton, Fumin Chang, John T. Lee, Richard A. Franklin, Linda S. Steelman, James A. McCubrey

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


FDC-P1 hematopoietic cells were conditionally transformed to grow in response to ΔB Raf:ER, ΔRaf-1:ER or ΔA-Raf:ER in which the hormone binding domain of the estrogen receptor (ER) was linked to the N-terminal truncated (Δ) Raf genes. When these cells were deprived of IL-3 or β-estradiol for 24 hrs, they exited the cell cycle and underwent apoptosis. FD/ΔRaf-1:ER and FD/ΔA-Raf:ER, but not FD/ΔB-Raf:ER cells, were readily induced to re-enter the cell cycle after addition of β-estradiol or IL-3. Deprived FD/ΔRaf-1:ER, but not FD/ΔB-Raf:ER cells, expressed activated forms of MEK1 and ERK after β-estradiol or IL-3 stimulation. Insulin or β-estradiol alone did not induce FD/ΔB-Raf:ER cells to re-enter the cell cycle, whereas cell cycle entry was observed upon their co-addition. Apoptosis was prevented in FD/ΔB-Raf:ER cells when they were cultured in the presence of IL-3 or β-estradiol, whereas they underwent apoptosis in their absence. Insulin by itself did not prevent apoptosis, however, upon ΔB-Raf:ER or ΔRaf-1:ER activation and addition of insulin, more than an additive effect was observed in both lines indicating that these pathways synergized to prevent apoptosis. Raf isoforms differ in their abilities to control apoptosis and cell cycle progression, and B-Raf requires insulin-activated pathways for full antiapoptotic and proliferative activity.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalCell Cycle
Issue number2
StatePublished - Feb 2004


  • Apoptosis
  • B-Raf
  • Cell cycle progression
  • PI3K
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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