In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breas...

We recently identified brain-derived neurotrophic factor (BDNF) in the dorsal striatum to be a major component of a homeostatic pathway controlling ethanol consumption. We hypothesized that ethanol-mediated activation of the BDNF signaling cascade is required for the ethanol-related function of the neurotrophic factor. Here, we demonstrate that exposure of striatal neurons to ethanol results in...

Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the...

MAP kinase stimulation is a key signaling event in the AT1 receptor (AT1R)-mediated chronic stimulation of tyrosine hydroxylase and norepinephrine transporter in brain neurons by angiotensin II (Ang II). In this study, we investigated the involvement of MAP kinase in AT1R phosphorylation to further our understanding of these persistent neuromodulatory actions of Ang II. Ang II caused a time-dep...

CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25- T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potentia...

The mitogen-activated protein (MAP) kinase signaling pathways help to mediate the hypertrophic response of the pressure-loaded adult heart, although their importance in fetal myocardium is less known. The goal of this study was to determine the role the MAP kinase signaling pathways play in regulating the response of the fetal heart to a pressure load. Aortic (Ao) and pulmonary artery (PA) band...

The L1 adhesion molecule regulates axon growth and is mutated in the X-linked mental retardation syndrome CRASH (acronym for corpus callosum agenesis, retardation, aphasia, spastic paraplegia, hydrocephalus). A novel role for L1 as a potentiator of neuronal cell migration to extracellular matrix proteins through beta1 integrins and intracellular signaling to mitogen-activated protein (MAP) kina...

Talking about thyroid carcinomas leaves a fairly wide slope, in which it should be considered not only the variants and their clinical frequency, but mutant genetic finding that gives preamble to malignancy, its variability, histological as well prognosis. It is important note most frequent carcinoma population papillary, with an index greater than 80% of all cases, being rare pediatrics. The p...

The interaction of macrophages with infectious agents leads to the activation of several signaling cascades, including mitogen-activated protein (MAP) kinases, such as p38. We now demonstrate that p38 MAP kinase-mediated responses are critical components to the immune response to Borrelia burgdorferi. The pharmacological and genetic inhibition of p38 MAP kinase activity during infection with th...

In diabetic retinopathy, endothelial cell apoptosis is paradoxically increased despite upregulation of the potent pro-survival factor VEGF. We tested the hypothesis that elevated glucose levels disrupt VEGF's pro-survival function via peroxynitrite-mediated alteration of the Akt-1/p38 MAP kinase signaling pathway by studies of retinal endothelial cells in vitro. High glucose or exogenous peroxy...