Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BLK mouse fibroblasts (H-2b) were genetically engineered to express costimulatory B7.1 and interleukin-2 (BLK/IL2/B7.1). The BLK/IL2/B7.1 cells were then pulsed with an ovalbumin (OVA) epitope as a model antigen (Ag) (BLK/IL2/B7.1/OVA), and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H-2b). The genetically engineered fibroblasts lacking one or two of three factors (interleukin-2, B7.1, and OVA) were constructed and used as controls. Immunization with the BLK/IL2/B7.1/OVA cells induced strong cytotoxic activities against OVA-expressing EL4 (EG7) tumor cells, but not against other H-2b tumor cells, such as EL4, C1498 and B16F1 cells. The magnitude of the cytotoxic response in mice with the BLK/IL2/B7.1/OVA cells was significantly higher than the response in mice immunized with any other cell constructs. CD8+ T cells with OVA-specific cytotoxic activities were predominant in mice immunized with the BLK/IL2/B7.1/OVA cells. Furthermore, immunization with the BLK/IL2/B7.1/OVA cells significantly prolonged the survival of mice, compared with any other cell constructs, when the mice were challenged with EG7 tumor cells at 2 weeks postimmunization. Induction of antitumoral CTL immunity by the BLK/IL2/B7.1/OVA cells was independent of host Ag-presenting cells and of CD4+ T-cell and natural killer 1.1+ cell help. These results suggest that fibroblasts can be genetically modified to efficient Ag-presenting cells for the induction of an Ag-specific CTL response.
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PMID:Genetically engineered fibroblasts with antigen-presenting capability: efficient induction of an antigen-specific cytotoxic T-lymphocyte response and protection against tumor development in vivo. 1088 16

In each of two experiments, rats were pre-exposed to two flavoured solutions, saline-lemon and sucrose-lemon. For group ALT, trials with one solution alternated with trials with the other. Group BLK received all trials with one solution in a block, before any trials with the other. An associative theory suggests that the alternating, but not the blocked, schedule would establish an inhibitory association between sucrose and saline. To provide a retardation test of this inhibition, some animals in each group were then given a single pairing of saline and sucrose, experienced sodium depletion, and were finally tested for their consumption of sucrose. Sodium depletion increased consumption of sucrose more in group BLK than in group ALT. In groups given no saline-sucrose pairing, sodium depletion had only a small effect on sucrose consumption, which was the same in both groups. After multiple pairings of saline and sucrose, sodium depletion had an equally large effect on sucrose consumption in both ALT and BLK groups. These results imply that alternating pre-exposure to two compound solutions does establish an inhibitory association between their unique elements, and thus provide support for an associative theory of perceptual learning.
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PMID:Evidence for inhibitory associations between the unique elements of two compound flavours. 1139 38

To examine the effect of exercise and adrenergic blockade on lymphocyte cytokine production, six men ingested either a placebo (control) or an alpha- (prazosin hydrochloride) and beta-adrenoceptor antagonist (timolol malate) capsule (blockade, or BLK) 2 h before performing 19 +/- 1 min of supine bicycle exercise at 78 +/- 3% peak pulmonary uptake. Blood was collected before and after exercise, stimulated with phorbol 12-myristate 13-acetate and ionomycin, and surface stained for T (CD3(+)) and natural killer [NK (CD3(-)CD56(+))] lymphocyte surface antigens. Cells were permeabilized, stained for the intracellular cytokines interleukin (IL)-2 and interferon (IFN)-gamma, and analyzed using flow cytometry. BLK had no effect on the resting concentration of stimulated cytokine-positive T and NK lymphocytes or the amount of cytokine they were producing. Exercise resulted in an increase (P < 0.05) in the concentration of stimulated T and NK lymphocytes producing cytokines in the circulation, but these cells produced less (P < 0.05) cytokine post- compared with preexercise. BLK attenuated (P < 0.05) the elevation in the concentration of lymphocytes producing cytokines during exercise; however, BLK did not affect the amount of IL-2 and IFN-gamma produced. These results suggest that adrenergic stimulation contributes to the exercise-induced increase in the concentration of lymphocytes in the circulation; however, it does not appear to be responsible for the exercise-induced suppression in cytokine production.
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PMID:Effect of adrenergic blockade on lymphocyte cytokine production at rest and during exercise. 1154 60

Keratolytic winter erythema is an autosomal dominant skin disorder characterised by erythema, hyperkeratosis, and peeling of the skin of the palms and soles, especially during winter. The keratolytic winter erythema locus has been mapped to human chromosome 8p22-p23. This chromosomal region has also been associated with frequent loss of heterozygosity in different types of cancer. To identify positional candidate genes for keratolytic winter erythema, a BAC contig located between the markers at D8S550 and D8S1695 was constructed and sequenced. It could be extended to D8S1759 by a partially sequenced BAC clone identified by database searches. In the 634 404 bp contig 13 new polymorphic microsatellite loci and 46 single nucleotide and insertion/deletion polymorphisms were identified. Twelve transcripts were identified between D8S550 and D8S1759 by exon trapping, cDNA selection, and sequence analyses. They were localised on the genomic sequence, their exon/intron structure was determined, and their expression analysed by RT-PCR. Only one of the transcripts corresponds to a known gene, encoding B-lymphocyte specific tyrosine kinase, BLK. A putative novel myotubularin-related protein gene (MTMR8), a potential human homologue of the mouse acyl-malonyl condensing enzyme gene (Amac1), and two transcripts showing similarities to the mouse L-threonine 3-dehydrogenase gene and the human SEC oncogene, respectively, were identified. The remaining seven transcripts did not show similarities to known genes. There were no potentially pathogenic mutations identified in any of these transcripts in keratolytic winter erythema patients.
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PMID:Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759. 1189 52

Rats were exposed to two compound solutions, saline-lemon and sucrose-lemon. In Group ALT, trials with one solution alternated with trials with the other. Group BLK received all trials with one solution before any trials with the other. Previous retardation tests had implied that only alternating exposure would establish sucrose as an inhibitor of saline. To provide a complementary summation test for this inhibition, in Experiment 1, all the animals received pairings of peppermint and saline and were tested for consumption of peppermint-sucrose under sodium depletion. Consumption was increased by sodium depletion only in Group BLK. In Experiment 2, a retardation test was used to show that presentation of saline-lemon before sucrose-lemon on each exposure day would establish sucrose as an inhibitor of saline. Neither exposure to sucrose-lemon before saline-lemon nor alternating exposure to sucrose and saline alone had the same effect. These results provide support for an associative theory of perceptual learning that suggests that exposure to complex stimuli aids later discrimination partially as a result of establishing inhibitory associations between their unique elements.
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PMID:Alternating exposure to two compound flavors creates inhibitory associations between their unique features. 1239 86

Mouse mammary gland cDNA library was screened to search for BLK-interacting protein using yeast two-hybrid system, and a mouse DNA amplified in mammary carcinoma 1 (mDAM1) was obtained. mDAM1 cDNA contained a full coding region of 678bp encoding 225 amino acids with the predicted molecular mass of 26kDa. Comparison of the mouse to human DAM1 revealed 90 and 100% identities at the nucleotide and protein levels, respectively. A single 1.5kb transcript for mDAM1 was expressed in NMuMG mouse mammary epithelial cells. Through in vitro protein binding assay, interaction between mDAM1 and BLK was also confirmed. NMuMG cells, stably transfected and expressing mDAM1, promoted cell death under serum starvation condition. Transient coexpression of mDAM1 and BLK showed increased cell death compared to BLK expression alone in NMuMG cells. These results indicate that mDAM1 promotes mammary epithelial cell death and pro-apoptotic function of BLK.
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PMID:Mouse DAM1 regulates pro-apoptotic activity of BLK in mammary epithelial cells. 1240 57

B-cell-specific plasma-membrane proteins are potential targets for either small molecule or antibody-based therapies. We have sought to annotate proteins expressed at the cell surface membrane in patients with chronic lymphocytic leukemia (CLL) using plasma-membrane-based proteomic analysis to identify previously uncharacterized and potentially B-cell-specific proteins. Proteins from plasma-membrane fractions were separated on one-dimensional gels and trypsinized fractions subjected to high-throughput MALDI-TOF mass spectrometry. Using this method, many known B-cell surface antigens were detected, but also known proteins not previously described in this disease or in this cellular compartment, including cell surface receptors, membrane-associated enzymes and secreted proteins, and completely unknown proteins. To validate the method, we show that BLK, a B-cell-specific kinase, is located in the CLL-plasma-membrane fraction. We also describe two novel proteins (MIG2B and B-cell novel protein #1, BCNP1), which are expressed preferentially in B cells. MIG2B is in a highly conserved and defined gene family containing two plasma-membrane-binding ezrin/radixin/moesin domains and a pleckstrin homology domain; the Caenorhabditis elegans homolog (UNC-112) is a membrane-associated protein that colocalizes with integrin at cell-matrix adhesion complexes. BCNP1 is a completely unknown protein with three predicted transmembrane domains, with three alternatively spliced final exons. Proteomic analysis may thus define new potential therapeutic targets.
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PMID:Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B. 1288 50

To assess the role of arterial baroreflex control in muscle blood flow (MBF) and voluntary locomotion, mean arterial pressure (MAP), MBF, and electromyograms (EMGs) were measured in freely moving mice before (CNT) and after blocking the afferent or efferent pathway of arterial baroreflexes, carotid sinus denervation (CSD), or intraperitoneal administration of phentolamine (BLK), respectively. MAP was measured through a catheter placed in the femoral artery. MBF was measured with a needle-type laser-Doppler flowmeter and recorded through a low-pass filter with an edge frequency of 0.1 Hz. The frequency and duration of locomotion were judged from EMG recordings in the hindlimb. These probes were implanted at least 2 days before the measurements. Muscle vascular conductance (MVC = MBF/MAP) in all groups started to rise within 1 s after the onset of locomotion, but the increasing rate in CSD and BLK was significantly higher than in CNT for the first 9 s (P < 0.001). MAP in CSD and BLK significantly decreased below the baseline within 1 s and this was highly correlated with the increase in MVC for the first 9 s (R2 = 0.842, P < 0.001), whereas MAP in CNT increased significantly 8 s after the onset of locomotion. Although the total period of movement in a free-moving state for 60 min was not significantly different between CNT and CSD (P > 0.1), the frequency of movement with a short duration of 0.1-0.4 min was higher in CSD than in CNT (P < 0.001), which was highly correlated with the reduction in MAP accompanying each period of movement (R2 = 0.883, P < 0.01). These results suggest that arterial baroreflexes suppress vasodilatation in contracting muscle to maintain MAP at the onset of voluntary locomotion, and are necessary to continue a given duration of locomotion in mice.
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PMID:Arterial baroreflex control of muscle blood flow at the onset of voluntary locomotion in mice. 1293 92

This study examined the effect of combined alpha- and beta-adrenergic blockade on glucose kinetics during intense exercise. Six endurance-trained men exercised for 20 minutes at approximately 78% of their peak oxygen consumption (Vo(2)) following ingestion of a placebo (CON) or combined alpha- (prazosin hydrochloride) and beta- (timolol maleate) adrenoceptor antagonists (BLK). Plasma glucose increased during exercise in CON (0 minutes: 5.5 +/- 0.1; 20 minutes: 6.5 +/- 0.3 mmol. L(-1), P <.05). In BLK, the exercise-induced increase in plasma glucose was abolished (0 minutes: 5.7 +/- 0.3; 20 minutes: 5.7 +/- 0.1 mmol. L(-1)). Glucose kinetics were measured using a primed, continuous infusion of [6,6-(2)H] glucose. Glucose production was not different between trials; on average these values were 25.3 +/- 3.9 and 30.9 +/- 4.4 micromol. kg(-1). min(-1) in CON and BLK, respectively. Glucose uptake during exercise was greater (P <.05) in BLK (30.6 +/- 4.6 micromol. kg(-1). min(-1)) compared with CON (18.4 +/- 2.5 micromol. kg(-1). min(-1)). In BLK, plasma insulin and catecholamines were higher (P <.05), while plasma glucagon was unchanged from CON. Free fatty acids (FFA) and glycerol were lower (P <.05) in BLK. These findings demonstrate that adrenergic blockade during intense exercise results in a blunted plasma glucose response that is due to enhanced glucose uptake, with no significant change in glucose production.
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PMID:Regulation of glucose kinetics during intense exercise in humans: effects of alpha- and beta-adrenergic blockade. 1466 66

The aim of this study was to investigate the changes in expression pattern of the most important genes connected with apoptosis in proliferative apoptotic lesions (hyperplasia, adenoma), applying cDNA microarray technique, in order to promote the possible diagnostic or therapeutic utilisation of any difference in gene expression compared to the healthy (normal) parathyroid gland. Samples were taken from surgically removed 2 hyperplasias, 2 adenomas and 2 normal parathyroid glands. The Apoptosis Gene Array (Superarray) was used. This contains 112 genes, in tetraspot arrangement. The probes measured 250-600 base pairs. Streptavidin was bound to the array. CDP Star TM chemiluminescent substrate was used for detection. The samples deriving from hyperplasia or adenoma were compared to samples from normal parathyroid glands. The following genes were overexpressed in both hyperplasia and adenoma: CHEK1, ATM, BCL-XL, FAS, TNF, cIAP1, TRAIL, FADD, CASP 4,5,6,8, CD120b, CD137, LTA, TANK, TARF2, CAD, LIGHTR, DR3LG. CASP1,10, BFAR, BOD, BCL2L2, TRANCE were underexpressed in both hyperplasia and adenoma. Genes overexpressed only in hyperplasia were: MDM2, MCL1, BCL2A1, BLK, RIPK2, CD40LG, TRAF5, HUS1, BNIP3. Underexpressed only in hyperplasia: BOK, CIDEA, TRAF1, TRIP. Overexpressed only in adenoma: APOLLON, RIPK1, LTB, LTBR, CASP2,13, cIAP2, CIDEB. Underexpressed only in adenoma: TRAF4 and FASLG. Overexpresion or underexpression meant 1.5-fold difference from normal average values. As a result of this study, both pro-apoptotic and antiapoptotic genes were identified in hyperplasia and adenoma of the parathyroid gland. It seems that increased proliferation is connected also with increased apoptotic activity, but tumor cell candidates are able to survive, by activation of signal pathways resulting in overexpresion of anti-apoptotic genes.
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PMID:[Changes in gene expression in the course of proliferative processes in the parathyroid gland]. 1688 77


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