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Transactivation joins multiple tracks to the ERK/MAPK cascade

Reinhard Wetzker1, Frank-D Böhmer

  • 1Institute for Molecular Cell Biology, Jena University Hospital, Drackendorfer Strasse 1, D-07747 JENA, Germany. i5rewe@rz.uni-jena.de

Nature Reviews. Molecular Cell Biology
|August 19, 2003
PubMed

Insights

G-protein-coupled receptors (GPCRs) can activate the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. A multi-track model may explain the complex signaling puzzles observed in GPCR transactivation studies.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • G-protein-coupled receptors (GPCRs) are key cellular regulators.
  • GPCR activation can influence other signaling pathways, including receptor tyrosine kinases (RTKs).
  • The extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway is a critical downstream signaling cascade.

Purpose of the Study:

  • To investigate the signaling mechanisms linking GPCRs to the ERK/MAPK pathway.
  • To address the complexities and unresolved questions arising from the 'transactivation' model.
  • To propose an alternative model for understanding GPCR-ERK/MAPK signaling.

Main Methods:

  • Review and analysis of existing literature on GPCR signaling.
  • Examination of experimental data supporting transactivation mechanisms.
  • Conceptual development of a multi-track signaling model.

Main Results:

  • Observed cross-talk between GPCRs and RTKs leading to ERK/MAPK activation.
  • Identified limitations and inconsistencies with a simple linear transactivation model.
  • Proposed a 'multi-track' model to accommodate diverse signaling outcomes.

Conclusions:

  • The 'transactivation' model alone may not fully explain GPCR-mediated ERK/MAPK pathway activation.
  • A 'multi-track' model offers a more comprehensive framework for understanding GPCR signaling to ERK/MAPK.
  • This revised model may resolve existing puzzles in the field of GPCR signaling.

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