Raf-1 kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, suppresses metastasis in a number of cancer types, including colorectal carcinoma (CRC); thus, RKIP downregulation significantly contributes to CRC invasiveness and metastatic potential. However, our previous study demonstrated that RKIP-positive tumors in CRC patients are...

Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors (PERK, ATF6, and IRE1) implement the UPR. PERK phosphorylation of the α subunit of...

Mutations in rhodopsin, the light-sensitive protein of rod cells, are the most common cause of dominant retinitis pigmentosa (RP), a type of inherited blindness caused by the dysfunction and death of photoreceptor cells. The P23H mutation, the most frequent single cause of RP in the USA, causes rhodopsin misfolding and induction of the unfolded protein response (UPR), an adaptive ER stress resp...

BACKGROUND Vascular calcification is a common feature in patients with chronic kidney disease (CKD). CKD increases serum levels of tumor necrosis factor-α (TNFα), a critical mediator of vascular calcification. However, the molecular mechanism by which TNFα promotes CKD-dependent vascular calcification remains obscure. The purpose of the present study was to investigate whether TNFα-induced vasc...

Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases of familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) and activates the unfolded protein response (UPR), suggesting that ER stress is involved in the pathogenesis of FALS. We used a genetic approach...

Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident...

D ietary zinc deficiency has been associated with memory impairment but the mechanisms underlying this effect remain unclear. The divalent cation zinc is one of the most abundant trace elements in the body and plays myriad functional roles (1). Although the vast majority of zinc is tightly bound to proteins, a pool of zinc in the mammalian forebrain is selectively stored in and released from gl...

Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK...

The protein kinase PERK couples protein folding in the endoplasmic reticulum (ER) to polypeptide biosynthesis by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha), attenuating translation initiation in response to ER stress. PERK is highly expressed in mouse pancreas, an organ active in protein secretion. Under physiological conditions, PERK was partial...

The phosphorylation of extracellular signal-regulated kinase (pERK) in DRG and dorsal horn neurons is induced by the C-fiber electrical stimulation to the peripheral nerve. The present study was designed to investigate the expression and modulation of pERK in the rat dorsal horn neurons produced by repetitive electrical stimulation, and its involvement in the electrophysiological activity of do...