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Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors

R A Hipskind1, D Büscher, A Nordheim

  • 1Institute for Molecular Biology, Hannover Medical School, Germany.

Genes & Development
|August 1, 1994
PubMed

Insights

Two distinct signaling pathways regulate ternary complex factors (TCFs) involved in gene activation. One pathway, dependent on Ras and mitogen-activated protein kinase (MAPK), modifies TCF/Elk-1, while another targets TCF/SAP-1 independently.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Extracellular signals activate immediate early genes like c-fos and egr-1 via ternary complex factors (TCFs).
  • Distinct TCFs, including Elk-1 and SAP-1, are involved in mediating this transcriptional activation.
  • Understanding the specific signaling pathways controlling TCF modification is crucial for deciphering gene regulation.

Purpose of the Study:

  • To investigate the distinct signaling pathways responsible for the modification of TCF/Elk-1 and TCF/SAP-1.
  • To elucidate the roles of Ras and mitogen-activated protein kinase (MAPK) in TCF regulation.
  • To differentiate the signaling mechanisms upstream of TCF/Elk-1 and TCF/SAP-1.

Main Methods:

  • Utilized BAC-1 macrophages and fibroblasts for experimental analysis.
  • Employed protein-DNA complex retardation assays to study TCF modifications.
  • Investigated the effects of MAPK activation, Ras mutants, PKC down-regulation, and Gi protein inhibition on TCF signaling.

Main Results:

  • TCF/Elk-1 hyperphosphorylation correlated with MAPK activation and c-fos/egr-1 induction, while TCF/SAP-1 complexes showed slower decay.
  • MAPK activation was essential for TCF/Elk-1 modification in vitro, but not for TCF/SAP-1.
  • Ras-dependent and MAPK-dependent signaling specifically targeted TCF/Elk-1, leaving TCF/SAP-1 modification unaffected.

Conclusions:

  • Two separate signaling pathways regulate distinct TCFs: one Ras/MAPK-dependent pathway converges on TCF/Elk-1.
  • A second pathway targets TCF/SAP-1 independently of Ras and MAPK.
  • These findings reveal differential regulation of TCFs, providing insights into c-fos and egr-1 gene activation mechanisms.

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