MAP kinase phosphatase-1 (MKP-1) controls nuclear MAP kinase activity with important consequences on cell growth or apoptosis. MKP-1 transcription is initiated constitutively but elongation is blocked within exon 1. It is unclear how induction of MKP-1 is controlled. Here, we report that the transcriptional elongation factors P-TEFb, DSIF and NELF regulate MKP-1 transcription in the pituitary G...

We have isolated a cDNA homologous to known dual-specificity phosphatases from a mouse macrophage cDNA library and termed it MKP-M (for mitogen-activated protein kinase phosphatase isolated from macrophages). Three other presumed splice variant isoforms have also been identified for MKP-M. The longest and most abundant mRNA contains an open reading frame corresponding to 677 amino acids and pro...

PURPOSE An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). T...

BACKGROUND Studies suggest that brain-derived neurotrophic factor (BDNF) exerts effects on the neuronal function of hippocampal neurons and increases hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, which causes depressive behaviors in rat or mouse. Here we focus on the change of serum MKP-1, BDNF, testosterone (T), and estradiol (E2) levels, in order to test the h...

Vascular smooth muscle contraction is primarily regulated by phosphorylation of myosin light chain. There are also modulatory pathways that control the final level of force development. We tested the hypothesis that protein kinase C (PKC) and mitogen-activated protein (MAP) kinase modulate vascular smooth muscle activity via effects on MAP kinase phosphatase-1 (MKP-1). Swine carotid arteries we...

Septic shock is a leading cause of morbidity and mortality. However, genetic factors predisposing to septic shock are not fully understood. Excessive production of proinflammatory cytokines, particularly tumor necrosis factor (TNF)-alpha, and the resultant severe hypotension play a central role in the pathophysiological process. Mitogen-activated protein (MAP) kinase cascades are crucial in the...

We have previously found that hypoxia stimulates proliferation of vascular fibroblasts through Galphai-mediated activation of ERK1/2. Here, we demonstrate that hypoxia also activates the atypical protein kinase Czeta (PKCzeta) isozyme and stimulates the expression of ERK1/2-specific phosphatase, MAP kinase phosphatase-1 (MKP-1), which attenuates ERK1/2-mediated proliferative signals. Replicatio...

Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, ...

We consider the application of a new metaheuristic technique that we have proposed, known as PROBE (Population Reinforced Optimization Based Exploration), to the multiconstraint knapsack problem (MKP). In the current section, we begin by giving a brief introduction to PROBE; we then briefly review other metaheuristic approaches for the MKP. In Section 2, we describe our PROBE approach for the M...

Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incomplete...