Although much has been learned about the role of the amygdala in Pavlovian fear conditioning, relatively little is known about the signaling pathway involved in the acquisition of an active avoidance reaction. The aim of this study is to investigate the potentiating effects of the NO-guanylate cyclase activator YC-1 on learning and memory of shuttle avoidance test in rats. YC-1 enhanced the ind...

Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2 genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity (LOH). Recently, extracellular signal-regulated kinase (Erk) has been found activated in TSC lesions lacking TSC1 or TSC2 LOH. Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2...

Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and sur...

The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade contributes to synaptic plasticity and to long-term memory formation, yet whether MAPK/ERK controls activity-dependent gene expression critical for long-lasting changes at the synapse and what the events underlying transduction of the signal are remain uncertain. Here we show that induction o...

Spatiotemporal control is a common mechanism that modulates activity and function of signal transducers in the signaling network. We identified acetylation of CNK1 (connector enhancer of kinase suppressor of Ras-1) as a late step in the activation of CNK1 signaling, accompanied with prolonged stimulation of extracellular signal-regulated kinase (ERK). We identified the acetyltransferase CREB (c...

BACKGROUND Hyperthermia is a promising treatment for human lung cancer, but recurrence of the primary lesion is common, as the residual tumor becomes adapted to heat treatment and growth is induced by hypoxia-triggered HIF-1a expression. Here, we explored the effects of hyperthermia on HIF-1a expression, proliferation, and lung cancer angiogenesis. METHODS Human NSCLC NCI-H1650 and SCLC NCI-H...

c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of...

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract within the huntingtin protein (Htt). Identifying the pathways that are altered in response to the mutant protein is crucial for understanding the cellular processes impacted by the disease as well as for the rational development of effective pharmacological interventions. Here...

B23, a multifunctional nucleolar protein, is overexpressed in numerous cancers and is associated with tumorigenesis. However, the clinical significance and potential role of B23 in bladder urothelial carcinoma remains to be elucidated. The present study observed that the mRNA and protein expression levels of B23 were increased in bladder cancer cells and tissues. The overexpression of B23 contr...

Extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase pathway activity is regulated by the antagonist function of activating kinases and inactivating protein phosphatases. Sustained ERK pathway activity is commonly observed in human malignancies; however, the mechanisms by which the pathway is protected from phosphatase-mediated inactivation in the tumor tissue remain obs...