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Basic fibroblast growth factor-induced activation of novel CREB kinase during the differentiation of immortalized

J Y Sung1, S W Shin, Y S Ahn

  • 1Department of Pharmacology, Brain Research Institute, and Brain Korea 21 Projects for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

Basic fibroblast growth factor (bFGF) triggers a novel signaling pathway to activate CREB (cAMP response element-binding protein) in hippocampal cells. This pathway is crucial for cell differentiation and gene transcription.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Neuroscience

Background:

  • Growth factors regulate cell proliferation, differentiation, and survival by binding to cell surface receptors.
  • Signal transduction pathways relay extracellular signals to the nucleus, influencing gene expression.
  • The transcription factor CREB (cAMP response element-binding protein) plays a key role in these cellular processes.

Purpose of the Study:

  • To investigate the signaling mechanism by which basic fibroblast growth factor (bFGF) activates CREB in immortalized hippocampal progenitor cells (H19-7).
  • To identify the specific pathways involved in bFGF-induced CREB phosphorylation and subsequent gene transcription.

Main Methods:

  • Utilized immortalized hippocampal progenitor cells (H19-7).
  • Examined CREB phosphorylation at Ser(133) residue using bFGF and epidermal growth factor (EGF).
  • Assessed CRE-mediated gene transcription and cell differentiation.
  • Employed in vitro in-gel kinase assays to identify novel kinases.

Main Results:

  • bFGF induced prolonged phosphorylation of CREB at Ser(133), leading to increased CRE-mediated gene transcription and H19-7 cell differentiation.
  • Expression of a non-phosphorylatable CREB mutant (S133A) blocked bFGF-induced differentiation.
  • bFGF-induced CREB phosphorylation kinetics differed from EGF, suggesting a distinct pathway.
  • Known signaling pathways (MAPK, PKA, PKC, PI3K-p70S6K, CaMK, CK2) did not mediate bFGF-induced CREB phosphorylation.
  • A novel 120-kDa bFGF-inducible CREB kinase was identified.

Conclusions:

  • bFGF activates a novel signaling pathway in hippocampal progenitor cells that leads to CREB phosphorylation and activation.
  • This pathway is distinct from previously known signaling cascades.
  • The identified bFGF-inducible CREB kinase is a key component of this new signaling mechanism.
  • This discovery provides new insights into growth factor-mediated regulation of gene expression and cell differentiation.

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