Wild-type KRAS acts as a switch during signal transduction; however, somatic mutations that activate regulators and effectors of Ras proteins are common in tumor development and cancer [1-3]. In approximately 35%–42% of early colorectal cancer (CRC) patients, the KRAS mutation inhibits KRAS GTPase, resulting in a constitutive KRAS activation and, thus, activating a Ras/Raf signaling pathway. In...

OBJECTIVE Recent findings have shown that pharmacogenetic manipulations of the Ras-ERK pathway provide a therapeutic means to tackle l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID). First, we investigated whether a prolonged l-DOPA treatment differentially affected ERK signaling in medium spiny neurons of the direct pathway (dMSNs) and in cholinergic aspiny interneurons (ChIs) an...

The striatum is critical for learning and decision making; however, the molecular mechanisms that govern striatum function are not fully understood. The extracellular signal regulated kinase (ERK) cascade is an important signaling pathway that underlies synaptic plasticity, cellular excitability, learning and arousal. This review focuses on the role of ERK signaling in striatum function. ERK is...

The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate methods to interfere with TCR activation of the ERK cascade. The first approach...

The Transforming Growth Factor-Beta (TGF-β) family is involved in regulating a variety of cellular processes such as apoptosis, differentiation, and proliferation. TGF-β binding to a Serine/Threonine kinase receptor complex causes the recruitment and subsequent activation of transcription factors known as smad2 and smad3. These proteins subsequently translocate into the nucleus to negatively or...

A unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. We show that the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines, providing insight into the molecular deter...

In the mammalian visual system, retinal ganglion cell (RGC) projections from each eye, initially intermixed within the dorsal-lateral geniculate nucleus (dLGN), become segregated during the early stages of development, occupying distinct eye-specific layers. Electrical activity has been suggested to play a role in this process; however, the cellular mechanisms underlying eye-specific segregatio...

Although aldosterone influences a variety of cellular processes through nongenomic mechanisms, the significance of nongenomic pathways for aldosterone-induced regulation of epithelial function is not understood. Recently, we demonstrated that aldosterone inhibits transepithelial HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a nongenomic pathway. This inhibition is me...