Related Experiment Video
Updated: May 19, 2026

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
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.
Abstract:
The Ras/Raf/MEK/ERK is a conserved signalling pathway involved in the control of fundamental cellular processes. Despite extensive research, how this pathway can process a myriad of diverse extracellular inputs into substrate specificity to determine biological outcomes is not fully understood. It has been established that the ERK1/2 pathway is an integrative point in the control of the pituitary function exerted by various extracellular signals. In addition we previously established that the GTPases Ras and Rap1 play a key role in the regulation of ERK1/2-dependent prolactin transcription by EGF or the cAMP-dependent neuropeptide VIP. In this report, using the FRET-based biosensor of ERK activity (EKAR) in the pituitary GH4C1 cell line, we show that both EGF and VIP tightly control the spatiotemporal dynamic of activated ERK with different magnitude and duration. Importantly, we provide the first evidence of a differential control of cytoplasmic and nuclear pools of activated ERK by the GTPases Ras and Rap1. Ras is required for nuclear magnitude and duration of EGF-dependent ERK activation, whereas it is required for both VIP-activated cytoplasmic and nuclear ERK pools. Rap1 is exclusively involved in VIP-activated ERK nuclear pool. Moreover, consistent with the control of the nuclear pool of activated ERK by the GTPases, we observe the same differential role of Ras and Rap1 on ERK nuclear translocation triggered by EGF or VIP. Together these findings identify Ras and Rap1 as determinant partners in shaping nuclear and cytoplasmic ERK kinetics in response to EGF and VIP, which in turn should control pituitary secretion.
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.
Related Concept Videos
MAPK Signaling Cascades
The Ras Gene
Ras is a superfamily...
PI3K/mTOR/AKT Signaling Pathway
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
The JAK-STAT Signaling Pathway
Regulation of the Unfolded Protein Response

