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Sustained phosphorylation of mitogen-activated protein kinase is required for basic fibroblast growth factor-mediated

K Abe1, A Aoyagi, H Saito

  • 1Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Tokyo, Japan. abe@hoshi.ac.jp

Neurochemistry International
|January 4, 2001
PubMed

Insights

Basic fibroblast growth factor (bFGF) promotes axonal branching in neurons. Sustained activation of the mitogen-activated protein kinase (MAPK) cascade is essential for this bFGF-mediated process.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Basic fibroblast growth factor (bFGF) is known to promote axonal branching in cultured neurons.
  • The precise molecular mechanisms underlying bFGF's role in axonal development are not fully elucidated.

Purpose of the Study:

  • To investigate the involvement of the mitogen-activated protein kinase (MAPK) cascade in bFGF-induced axonal branching in rat hippocampal neurons.

Main Methods:

  • Primary cultures of rat hippocampal neurons were treated with recombinant human bFGF.
  • MAPK phosphorylation was assessed using Western blotting.
  • Specific MAPK kinase inhibitors (U0126 and PD98059) were used to block signaling pathways.
  • Axonal branch formation was quantified.

Main Results:

  • bFGF treatment led to concentration- and time-dependent phosphorylation of p44/42 MAPK, occurring rapidly and lasting up to 48 hours.
  • Inhibition of MAPK kinases with U0126 and PD98059 blocked both bFGF-induced p44/42 MAPK phosphorylation and axonal branching.
  • Delayed addition of MAPK inhibitors reduced p44/42 MAPK phosphorylation and halted further axonal branching.

Conclusions:

  • Sustained activation of the MAPK cascade is a critical requirement for bFGF-mediated axonal branch formation in hippocampal neurons.
  • This study highlights the role of the MAPK pathway as a key mediator of bFGF's effects on neuronal development.

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