Ras and Rap1 govern spatiotemporal dynamic of activated ERK in pituitary living cells

Caroline Zeiller1, Marie-Pierre Blanchard, Morgane Pertuit

  • 1Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344 cedex 15, Marseille, France.

Cellular Signalling
|September 4, 2012
PubMed

Insights

Ras and Rap1 GTPases differentially regulate the extracellular signal-regulated kinase (ERK) pathway in pituitary cells. This study reveals their distinct roles in controlling cytoplasmic and nuclear ERK activity, impacting pituitary function.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Endocrinology

Background:

  • The Ras/Raf/MEK/ERK pathway controls fundamental cellular processes, but its input-output mechanisms remain unclear.
  • ERK1/2 is a key regulator of pituitary function, integrating diverse extracellular signals.
  • Ras and Rap1 GTPases were previously shown to regulate ERK1/2-dependent prolactin transcription.

Purpose of the Study:

  • To investigate the spatiotemporal dynamics of activated ERK1/2 in response to EGF and VIP in pituitary cells.
  • To elucidate the differential roles of Ras and Rap1 in controlling cytoplasmic and nuclear ERK activation and translocation.

Main Methods:

  • Utilized a Förster Resonance Energy Transfer (FRET)-based biosensor of ERK activity (EKAR).
  • Employed the pituitary GH4C1 cell line for experiments.
  • Analyzed the effects of Epidermal Growth Factor (EGF) and Vasoactive Intestinal Peptide (VIP) on ERK activity.

Main Results:

  • EGF and VIP differentially control the magnitude and duration of ERK activation.
  • Ras GTPase is crucial for the nuclear magnitude and duration of EGF-dependent ERK activation.
  • Ras and Rap1 GTPases differentially regulate cytoplasmic and nuclear ERK pools activated by VIP.
  • Ras and Rap1 exhibit distinct roles in EGF- or VIP-triggered ERK nuclear translocation.

Conclusions:

  • Ras and Rap1 are key regulators shaping ERK kinetics in both cytoplasmic and nuclear compartments.
  • These differential regulatory roles of Ras and Rap1 in ERK signaling influence pituitary secretion.

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