Gonadotropin-releasing hormone receptors (GnRHR) mediate activation and nuclear translocation of the extracellular signal regulated kinases 1 and 2 (ERK) by phosphorylation on the TEY motif. This is necessary for GnRH to initiate transcriptional programmes controlling fertility, but mechanisms that govern ERK targeting are unclear. Using automated microscopy to explore ERK regulation in single ...

Inhibition of Mek/Erk signaling by pharmacological Mek inhibitors promotes self-renewal and pluripotency of mouse embryonic stem cells (ESCs). Intriguingly, Erk signaling is essential for human ESC self-renewal. Here we demonstrate that Erk signaling is critical for mouse ESC self-renewal and genomic stability. Erk-depleted ESCs cannot be maintained. Lack of Erk leads to rapid telomere shorteni...

Extracellular signal-regulated kinase (ERK) is a key effector of many growth signalling pathways. In this study, we visualise epidermal ERK activity in living mice using an ERK FRET biosensor. Under steady-state conditions, the epidermis occasionally revealed bursts of ERK activation patterns where ERK activity radially propagated from cell to cell. The frequency of this spatial propagation of ...

The phosphorylation cascade in the extracellular signal-regulated kinase (ERK) pathway is a versatile reaction network motif that can potentially act as a switch, oscillator or memory. Nevertheless, there is accumulating evidence that the phosphorylation response is mostly linear to extracellular signals in mammalian cells. Here we find that subsequent nuclear translocation gives rise to a swit...

The mitogen activated protein (MAP) kinase cascade, leading to extracellular-regulated kinase (ERK) activation, is a key regulator of cell growth and proliferation. The effects of ERK are mediated by differences in ERK signalling dynamics, including magnitude and duration. In vivo, ERK signalling is stimulated by both growth factors and adhesion signals. A model for adhesion-mediated ERK activa...

Human Intestine 407 cells respond to hypo-osmotic stress with a rapid stimulation of compensatory ionic conductances accompanied by a transient increase in the activity of the extracellular-signal-regulated protein kinases Erk-1 and Erk-2. In this study, we examined the upstream regulators of hypotonicity-induced Erk-1/Erk-2 activation and their possible role in cell-volume regulation. The hypo...

BACKGROUND Study of ERK activation has thus far relied on biochemical assays that are limited to the use of phospho-specific antibodies and radioactivity in vitro, and analysis of whole cell populations in vivo. As with many systems, fluorescence resonance energy transfer (FRET) can be utilized to make highly sensitive detectors of molecular activity. Here we introduce FRET-based ERK Activity S...

Several families of G protein-coupled receptors (GPCR) have been shown to activate extracellular signal-regulated kinase (ERK) in transfected cells and non-neuronal systems. However, little is known about GPCR activation of ERK in brain. Because ERK is an important component in the regulation of synaptic plasticity, in this study we examined ERK activation by three families of GPCR that respond...

Cluster of differentiation (CD)133 has been reported to be involved in the activation of the extracellular signal-regulated kinase (ERK) signaling pathway in different types of cancer cells. CD133 has been reported to be involved in the activation of the ERK signaling pathway in various cancer cells. Transforming growth factor (TGF)-β1 has also been reported to mediate the activation of the ERK...

β1-Adrenergic receptor autoantibodies are associated with deleterious consequences; however, the IgG3 subclass provides beneficial outcomes in human heart failure. β1AR autoantibody inhibits G-protein coupling, simultaneously activating ERK through G-protein–independent arrestin-dependent mechanisms.