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The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3

K Okazaki1, N Sagata

  • 1Division of Molecular Genetics, Institute of Life Science, Kurume University, Fukuoka, Japan.

The EMBO Journal
|October 16, 1995
PubMed

Insights

The Mos/MEK/ERK pathway stabilizes the c-Fos protein, enhancing cell transformation. This stabilization, crucial for oncogenic signaling, is mediated by specific phosphorylation events within c-Fos.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncogenesis

Background:

  • The Mos proto-oncogene product is a serine/threonine kinase activating ERK1/2 MAP kinases via MEK.
  • ERK activation by Mos is critical for oncogenic transformation of NIH 3T3 cells.

Purpose of the Study:

  • To investigate how the Mos/MEK/ERK pathway signals to the nucleus to activate target genes.
  • To determine the role of c-Fos stabilization in Mos-mediated oncogenic transformation.

Main Methods:

  • Investigated the metabolic stability of c-Fos in NIH 3T3 cells.
  • Analyzed Mos-induced phosphorylation sites on c-Fos (Ser362 and Ser374).
  • Utilized site-directed mutagenesis (Ser to Asp replacements) to assess functional impact.

Main Results:

  • Mos significantly enhances the metabolic stability and transforming efficiency of c-Fos.
  • Stabilization of c-Fos by Mos requires phosphorylation at Ser362 and Ser374.
  • ERK pathway activation is necessary and sufficient for c-Fos phosphorylation and stabilization.
  • Mutating Ser362/374 to Asp residues increased c-Fos stability and transforming efficiency independently of Mos.

Conclusions:

  • c-Fos stabilization by the Mos/MEK/ERK pathway plays a role in oncogenic signaling.
  • The ERK pathway may regulate cell fate and function by modulating c-Fos metabolic stability.

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