scholarly journals Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries

2013 ◽  
Vol 114 (2) ◽  
pp. 252-261 ◽  
Author(s):  
Nadi T. Wickramasekera ◽  
Debebe Gebremedhin ◽  
Koryn A. Carver ◽  
Padmanabhan Vakeel ◽  
Ramani Ramchandran ◽  
...  
Keyword(s):  
Protein Expression ◽  
Protein Phosphatase ◽  
Single Channel ◽  
Cerebral Arteries ◽  
Protein Phosphatase 5 ◽  
Dual Specificity ◽  
Arterial Constriction ◽  
Dual Specificity Protein Phosphatase ◽  
Specificity Protein

The present study examined the role of the dual-specificity protein phosphatase-5 (DUSP-5) in the pressure-induced myogenic responses of organ-cultured cerebral arterial segments. In these studies, we initially compared freshly isolated and organ-cultured cerebral arterial segments with respect to responses to step increases in intravascular pressure, vasodilator and vasoconstrictor stimuli, activities of the large-conductance arterial Ca2+-activated K+ (KCa) single-channel current, and stable protein expression of DUSP-5 enzyme. The results demonstrate maintained pressure-dependent myogenic vasoconstriction, DUSP-5 protein expression, endothelium-dependent and -independent dilations, agonist-induced constriction, and unitary KCa channel conductance in organ-cultured cerebral arterial segments similar to that in freshly isolated cerebral arteries. Furthermore, using a permeabilization transfection technique in organ-cultured cerebral arterial segments, gene-specific small interfering RNA (siRNA) induced knockdown of DUSP-5 mRNA and protein, which were associated with enhanced pressure-dependent cerebral arterial myogenic constriction and increased phosphorylation of PKC-βII. In addition, siRNA knockdown of DUSP-5 reduced levels of phosphorylated ROCK and ERK1 with no change in the level of phosphorylated ERK2. Pharmacological inhibition of ERK1/2 phosphorylation significantly attenuated pressure-induced myogenic constriction in cerebral arteries. The findings within the present studies illustrate that DUSP-5, native in cerebral arterial muscle cells, appears to regulate signaling of pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain.

scholarly journals The Dual-Specificity Protein Phosphatase Yvh1p Acts Upstream of the Protein Kinase Mck1p in Promoting Spore Development in Saccharomyces cerevisiae

1999 ◽  
Vol 181 (17) ◽  
pp. 5219-5224 ◽  
Author(s):  
Alexander E. Beeser ◽  
Terrance G. Cooper
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Phosphatase ◽  
Vegetative Growth ◽  
Nitrogen Starvation ◽  
Developmental Pathway ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase ◽  
Specificity Protein ◽  
Spore Maturation

ABSTRACT Diploid Saccharomyces cerevisiae cells induce YVH1 expression and enter the developmental pathway, leading to sporulation when starved for nitrogen. We show that yvh1 disruption causes a defect in spore maturation; overexpression of MCK1or IME1 suppresses this yvh1 phenotype. Whilemck1 mutations are epistatic to those in yvh1relative to spore maturation, overexpression of MCK1 does not suppress the yvh1 slow-vegetative-growth phenotype. We conclude that (i) Yvh1p functions earlier than Mck1p and Ime1p in the signal transduction cascade that regulates sporulation and is triggered by nitrogen starvation and (ii) the role of Yvh1p in gametogenesis can be genetically distinguished from its role in vegetative growth.

scholarly journals Immunohistochemical Expression of Dual-Specificity Protein Phosphatase 4 in Patients with Colorectal Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jongmin Sim ◽  
Kijong Yi ◽  
Hyunsung Kim ◽  
Hyein Ahn ◽  
Yumin Chung ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Colorectal Adenocarcinoma ◽  
Malignant Tumors ◽  
Male Gender ◽  
Rank Test ◽  
Log Rank Test ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase ◽  
Specificity Protein

The role of dual-specificity protein phosphatase 4 (DUSP4) appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P<0.001). Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P<0.001). DUSP4 expression was significantly correlated with older age (P=0.017), male gender (P=0.036), larger tumor size (P=0.014), nonmucinous tumor type (P=0.023), and higher T stage (P=0.040). Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P=0.008andP=0.003, resp., log-rank test) and male gender (P=0.017andP=0.049, resp., log-rank test). DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis.

Abstract 223: Zinc-finger Nuclease Knockout Of Dual-specificity Protein Phosphatase-5 Enhances Myogenic Response In Autoregulation Of Cerebral Blood Flow In Fhh.1bn Rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fan Fan ◽  
Aron M Geurts ◽  
Mallikarjuna R Pabbidi ◽  
David R Harder ◽  
Howard Jacob ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Protein Phosphatase ◽  
Genetic Background ◽  
Zinc Finger Nuclease ◽  
Brown Norway ◽  
Myogenic Response ◽  
Protein Phosphatase 5 ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase ◽  
Specificity Protein

We recently reported that the pressure-induced myogenic responses of afferent arteries (Af-Art) and middle cerebral arteries (MCAs) were impaired in the fawn hooded hypertensive (FHH) rats and were restored in FHH.1BN congenic strain in which chromosome 1 from the Brown Norway (BN) rats containing 11 genes including dual-specificity protein phosphatase-5 (Dusp5) was transferred into FHH genetic background. There are 4 single nucleotide polymorphisms (SNP) in Dusp5 in FHH as compared with BN rats, one of which causes G155R mutation. To determine whether Dusp5 contributes to the impaired vascular myogenic response in FHH rats, we created a Dusp5 knockout (KO) rats in the FHH.1BN genetic background using zinc-finger nuclease (ZFN) that introduced a premature stop codon at amino acid (AA) 121. The expression of Dusp5 in KO rats were significantly decreased and the level of phosphorylated ERK2 (p-ERK2) was significantly increased in multiple organs including liver, spleen and white blood cells (WBCs). The luminal diameter of the MCAs in FHH.1BN rats (n=12) decreased 20 ± 2 % when the perfusion pressure was increased from 40 to 140 mmHg, whereas it decreased 34 ± 7 % in Dusp5 KO rats (n=6) and increased 10 ± 4% in FHH strain (n=8). Autoregulation was markedly impaired and CBF increased by 54 ± 6% in FHH rats when MAP was increased from 100 to 160 mmHg. CBF was better autoregulated in FHH.1BN strain and Dusp5 KO rats increased by only 26 ± 3% and 12 ± 3% when MAP was increased over the same range. However, the range of autoregulation of CBF was extended in the FHH rats (n=7) in that CBF rose to 107 ± 6% in FHH.1BN rats (n=7) when pressure was increased to 190 mmHg versus 33 ± 4% in the Dusp5 KO animals (n=6). These results suggest that Dusp5 plays an important role in modulating of myogenic tone in the cerebral circulation. Unless the G155R mutation activates Dusp5 in FHH rats, it is unlikely that Dusp5 is responsible for the impaired myogenic response in FHH rats.

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