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Specific phosphorylation and activation of ERK1c by MEK1b: a unique route in the ERK cascade

Yoav D Shaul1, Gilad Gibor, Alexander Plotnikov

  • 1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Genes & Development
|August 5, 2009
PubMed

Insights

Mitogen-activated protein kinase (MAPK) signaling involves distinct pathways. Splice variants MEK1b and ERK1c mediate Golgi fragmentation during mitosis, separate from the classic MEK1/2-ERK1/2 route.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cell cycle regulation

Background:

  • Extracellular signal-regulated kinases (ERKs) are crucial for cellular processes, including mitosis.
  • ERK1c, an alternatively spliced ERK1 variant, promotes Golgi fragmentation during mitosis independently of ERK1 and ERK2.
  • Mitogen-activated protein kinase (MAPK)/ERK kinase 1b (MEK1b) is an alternatively spliced MEK1 variant previously thought to be inactive.

Purpose of the Study:

  • To investigate the activation mechanism of ERK1c.
  • To elucidate the role of MEK1b in regulating ERK1c activity.
  • To differentiate the functions of splice variants within the MAPK cascade during mitosis.

Main Methods:

  • Investigating the interaction and activation of MEK1b and ERK1c using molecular biology techniques.
  • Stimulating cells with nocodazole and epidermal growth factor (EGF) to assess pathway activation.
  • Analyzing Golgi fragmentation, mitotic rate, and progression in response to specific kinase activities.

Main Results:

  • MEK1b preferentially activates ERK1c, particularly upon nocodazole stimulation.
  • MEK1/2 primarily targets ERK1/2 in response to EGF.
  • Both MEK1b and ERK1c expression and activity increase during mitosis, enhancing Golgi fragmentation and mitotic rate.
  • MEK1 activity also rises in mitosis but promotes progression without altering Golgi structure.

Conclusions:

  • The ERK cascade bifurcates into two distinct signaling routes: the canonical MEK1/2-ERK1/2 pathway and the splice-variant MEK1b-ERK1c pathway.
  • Each pathway regulates specific cellular processes, demonstrating extended specificity within the MAPK cascade.
  • MEK1b-ERK1c signaling plays a critical role in mitotic Golgi fragmentation and mitotic rate.

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