Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of protein kinase C and A was studied in the erythrocytes of patients with essential hypertension (EH) and in spontaneously hypertensive rats (SHR, Okamoto-Aoki strain). Protein kinase C activity was also studied in the erythrocytes of patients with hypertension of renal origin. Protein kinase C activity in the lysate of erythrocytes of patients with EH and in SHR was found to be increased 1.6-2.0-fold as compared to that in normotensive controls. No notable differences in protein kinase A activity were observed between hypertensive and normotensive groups. In erythrocytes of patients with renal hypertension, no notable changes in protein kinase C activity were revealed.
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PMID:Activity of protein kinase C in erythrocytes in primary hypertension. 323 34

Activities of protein kinases A and C in erythrocyte cytoplasmic fraction purified by CM-Sephadex and DEAE-cellulose have been measured. Protein kinase C activity is shown to be 1.6-1.8-fold higher, as compared to controls, in essential hypertension, but remain unchanged in renal hypertension. Protein kinase A activity is slightly elevated in patients with essential hypertension, but the difference is not significant. It is suggested that the increase of protein kinase C activity, and perhaps some other activities as well, in essential hypertension may be a result of altered expression of protooncogenes with protein kinase activities.
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PMID:[Protein kinase A and C activity of erythrocytes in patients with essential hypertension]. 341 69

The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.
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PMID:Two point mutations within the adducin genes are involved in blood pressure variation. 817 Oct 25

1. beta-Adrenoceptor (beta-AR)-mediated vasodilation, which plays an important physiological role in the regulation of vascular tone, is decreased in two-kidney, one clip (2K-1C) renal hypertension. In this study, downstream pathways related to vascular beta-AR activation were evaluated in 2K-1C rats. 2. Relaxation responses to isoprenaline, forskolin and 8-Br-cAMP were diminished in aortas without endothelium from 2K-1C when compared to those in normotensive two kidney (2K). Basal adenosine-3',5'-monophosphate (cAMP), as well as isoprenaline-induced increase in cAMP levels, was not different between 2K and 2K-1C aortas. 3. Contractile responses to caffeine, after depletion and reloading of intracellular Ca(2+) stores, were greater in 2K-1C than in 2K. The presence of isoprenaline during the Ca(2+)-reloading period abolished the differences between groups by increasing caffeine contraction in 2K without changing this response in 2K-1C aortas. Inhibition of the sarcolemmal Ca(2+)ATPase with thapsigargin markedly attenuated isoprenaline vasodilation in both 2K and 2K-1C and abolished the differences between groups. 4. Blockade of ATP-sensitive K(+) channels (K(ATP)) channels with glibenclamide significantly decreased isoprenaline vasodilation in 2K-1C without affecting this response in 2K. Both vascular gene and protein expression of protein kinase A (PKA), as well as phosphoserine-containing proteins, were increased in 2K-1C vs 2K rats. 5. In conclusion, decreased isoprenaline vasodilation in 2K-1C hypertensive rats is related to impaired modulation of the sarcolemmal Ca(2+)ATPase activity. Moreover, K(ATP) channels may play a compensatory role on isoprenaline-induced relaxation in renal hypertension. Both Ca(2+)ATPase and K(ATP) channel functional alterations, associated with decreased beta-AR vasodilation, are paralleled by an upregulation of protein kinase A (PKA) and phosphoserine proteins expression.
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PMID:Changes in the vascular beta-adrenoceptor-activated signalling pathway in 2Kidney-1Clip hypertensive rats. 1500 2

Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine that binds to five G protein-coupled receptors. We discovered expression of DA type-1 receptors (D1Rs) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA (Food and Drug Administration) approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.
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PMID:Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer. 2647 16