Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primer extension experiments showed that the argR gene, encoding the arginine repressor in Salmonella typhimurium, is transcribed from a single promoter that is negatively regulated by arginine. A repressor overproducing strain was constructed and the repressor was purified to homogeneity. Gel filtration, sedimentation and cross-linking studies established that the native repressor is a hexamer of identical 17,000 Mr subunits. Gel retardation experiments indicate that the apparent dissociation constant for repressor/carAB operator is 6 x 10(-12) M. These experiments showed that arginine is essential for binding of the repressor to the DNA and that pyrimidine nucleotides have no significant effect on this binding. These results indicate that the effect of pyrimidines on expression of the arginine sensitive "downstream" carAB promoter is not directly mediated by the arginine repressor. These experiments also suggest that a single hexamer binds to the carAB operator, which carries two previously defined "ARG box" sequences that characterize operators for arg genes. Gel retardation experiments with DNA fragments carrying the individual ARG boxes showed that both boxes are required for effective binding of the hexameric repressor to the operator, indicating that the ARG boxes comprise a single binding site for the repressor. Analysis of the potential secondary structure of the arginine repressor does not reveal any of the recognizable structural motifs common to a number of DNA-binding proteins. A combination of DNase I, premethylation interference, depurination and hydroxyl radical footprinting techniques were employed to characterize the interactions of the repressor with the carAB operator, with the results suggesting that the repressor predominantly interacts with A.T residues in this region. Comparative DNA sequence analysis of the known arginine operators of enteric bacteria further indicates that the specificity of interaction may be based more on the precise distance between two defined A.T-rich regions rather than on the specific nucleotide sequence.
 ...
PMID:Characterization of the arginine repressor from Salmonella typhimurium and its interactions with the carAB operator. 158 85

Twenty obese and 20 lean LA/N-cp male rats and 20 male Sprague-Dawley rats were fed a diet containing either 54 percent sucrose or starch for six weeks. After a 14-16 hour fast, rats were killed. Liver and kidney enzyme activities were determined in the LA/N-cp rats while plasma urea and selected amino acids were determined in all rats. Liver glucose-6-phosphatase (G6PASE), fructose-1,6-bisphosphatase (FBPASE), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), glucokinase (GK), pyruvate kinase (PK), phosphofructokinase (PFK), glutamic-oxaloacetic-transaminase (GOT), glutamic-pyruvic transaminase (GPT), arginase (ARGASE), arginine-synthase (ARG-SYN) and ornithine transcarbamylase (OTC) levels were significantly affected by phenotype (obese greater than lean). All the above changes in enzyme levels were exaggerated by sucrose-feeding with the exception of PK, PFK, GOT, GPT, ARGASE and ARG-SYN. Kidney cortex G6PASE, PEPCK and ARGASE activities were higher in the obese rats as compared to the lean littermates. Sucrose feeding resulted in higher cortex G6PASE, FBPASE and PEPCK as compared to starch-fed rats. A phenotype effect was noted with plasma glutamate, urea, leucine, isoleucine and valine (obese greater than lean) and a diet effect was seen with aspartate, phenylalanine, leucine and valine (sucrose greater than starch) concentration. Sprague-Dawley rats had higher plasma urea and lower alanine than lean LA/N-cp males. Metabolic obesity in the LA/N-cp rat appears to involve an elevated capacity for pathways of glycolysis, gluconeogensis, lipogenesis and amino acid catabolism in the liver.
 ...
PMID:Effect of dietary carbohydrate on liver and kidney enzyme activities and plasma amino acids in the LA/N-cp rat. 204 12

In Escherichia coli, the arginine repressor, the product of the argR gene, in conjunction with L-arginine controls the synthesis of the enzymes of arginine biosynthesis. We describe the nucleotide sequence of the argR gene, including its control region, and show that formation of the repressor is autoregulated. The argR control region contains two promoters, one of which overlaps the operator site and, as with other arg genes, consists of two adjacent palindromic sequences ("ARG boxes"). The arginine repressor protein and an arginine repressor-beta-galactosidase fusion protein were purified, and the amino acid sequence of the N-terminal end of the repressor protein portion of the fusion protein was determined. Antibodies prepared against the fusion protein react with the repressor. The repressor is precipitable by L-arginine, which facilitates its purification. The native repressor is a hexamer with a molecular weight of 98,000; its monomeric subunit has a molecular weight of 16,500. To verify its properties postulated from genetic studies, we show that in the presence of L-arginine, repressor inhibits transcription of argF and binds to the ARG boxes of argF and argR.
 ...
PMID:Nucleotide sequence of the argR gene of Escherichia coli K-12 and isolation of its product, the arginine repressor. 311 42

The ventral and dorsal lobes of the rat prostate contain larger quantities of the aliphatic amines putrescine, spermidine and spermine and higher activities of the enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) than other accessory sex glands. In contrast, the coagulating glands and the seminal vesicles contain only small quantities of the amines but the highest activities of the arginase (ARG; EC 3.5.3.1). Lineweaver-Burk plots indicated that the Km-values for ARG in the coagulating gland and ODC in the ventral prostate lobe were 20 mM and 0.2 mM, respectively. Castration decreased ODC and ARG activities to 3 and 50% of control levels, respectively, after 3 days, whilst the Km-values were unaffected. Daily administration of 3 mg dihydrotestosterone (DHT) prevented these castrational changes. Oestrogen treatment alone had no effect on the activities of the enzymes, but appeared to exert a synergistic effect with androgen on the ODC. Administration of androgen to intact rats for 7 days caused a dose-related alteration in the ratios of the various amines, particularly the spermine: putrescine ratio. A minor but significant decrease was also recorded in the activity of the ODC, which was mirrored by an increase in the levels of putrescine in the tissue. The data suggest that androgen control of the polyamine pathway is biphasic, first stimulatory and later inhibitory with lesions occurring at the ODC, possibly via short loop feedback of its product putrescine, but also at subsequent enzymic steps in spermidine and spermine biosynthesis.
 ...
PMID:Androgen interaction with the polyamine system of the rat prostate. 368 84

The CSK-gene encodes an intracellular protein-tyrosine kinase (PTK). In contrast to members of the src-family, an autophosphorylation site corresponding to Tyr416, as well as the equivalent of the regulatory Tyr527 in p60c-src are missing in the amino acid sequence deduced from the gene. CSK phosphorylates other members of the src-family of tyrosine kinases at their regulatory carboxy-terminus. By regulating the activity of these kinases, CSK may play an important role in cell growth and development. Here we describe the structure of the human CSK gene. The entire coding region spans a genomic distance of only 4.9 kb. It encompasses 12 exons ranging between 66 and 220 bp in size. The introns between coding exons vary between 76 and 920 bp in length. An exon coding for the 5'-untranslated region of CSK is separated from the first coding exon by an intron of more than 6400 bp. Based on comparisons of sequence homologies within the catalytic domains, the intracellular PTKs are divided into the src-family, the fes/fer- and the abl/arg-group. The genomic structure of four members of the SRC-family revealed nearly identical exon/intron boundaries within the catalytic domain of this family. They differ from those described for FES. Comparing the genomic structure of CSK with the exon/intron organisation of both, it is obvious that the exon/intron boundaries are in common either with those of the SRC-type or the FES boundaries. This intermediate exon/intron structure of CSK between FES and the SRC-family agrees with the position of CSK in a phylogenetic tree based on sequence homology within the kinase domain.
 ...
PMID:Characterization of the human CSK locus. 768 31

In Escherichia coli K12, formation of the enzymes of arginine biosynthesis are controlled by arginine, with complete repression during growth with added arginine, severe repression (about 95%) during growth without added arginine and complete derepression during arginine-limited growth. In E. coli B, the degree of repression is not correlated with arginine concentrations. Under all conditions of growth enzyme formation is repressed, with repression being somewhat less in a medium with arginine than in a medium without arginine. These differences in repressibility between the two strains have been shown previously to be due to the presence of different alleles of argR, the gene for the arginine repressor. Here we have compared the binding of the two repressors to the operator sites of argF (ARG boxes). In DNase I footprinting and gel retardation experiments with argF ARG boxes we have shown that the arginine repressor of E. coli K12 bound to arginine (ArgRK-arg) has a greater affinity than the arginine repressor of E. coli B bound to arginine (ArgRB-arg), whereas free ArgRB (ArgRBf) has a much stronger affinity than free ArgRK (ArgRKf). The stronger binding of ArgRBf can explain the repression seen in E. coli B during arginine-limited growth and indicates that ArgRBf, but not ArgRKf, is able to repress enzyme synthesis under physiological conditions. The weaker repression of E. coli B than of E. coli K12 seen in the presence of arginine can be explained by the lower affinity of ArgRB-arg for operator sites as compared to ArgRK-arg. Another contributing cause for the weaker repression is the reduction of ArgRBf concentration due to autoregulation of the gene for the repressor. Thus the combined effects of repression by ArgRBf, but not ArgRKf, with the weaker repression by ArgRB-arg as compared to ArgRK-arg, convert the arginine dependent regulation in E. coli K12 to arginine independent regulation in E. coli B.
 ...
PMID:Explanation for different types of regulation of arginine biosynthesis in Escherichia coli B and Escherichia coli K12 caused by a difference between their arginine repressors. 828 43

Mutations in arg-13 result in slow growth in minimal medium and can suppress mutations in carbamyl phosphate synthase-aspartate carbamyl transferase within the pyrimidine pathway; the exact biochemical function of the gene product is unknown. To understand the role of arg-13 in arginine metabolism, cosmids rescuing growth in arg-13 mutants were cloned and mapped to the position of arg-13 on LG IR. Northern analysis showed the arg-13 message to contain approximately 2100 nt, although a 1.4-kb genomic fragment truncated at the 5' and 3' ends of the gene encodes a shortened transcript that can rescue arg-13 function. Expression of mRNA arising from the mutant arg-13 gene is induced by arginine starvation, although wild type (arg-13+) is not derepressed in minimal medium. The sequence of the arg-13 gene shows ARG-13 to be a member of the mitochondrial carrier superfamily with three repeats of a approximately 100-amino acid domain, six putative membrane spanning regions, and three copies of the mitochondrial carrier consensus pattern. This information plus available and new nutritional data are consistent with the hypothesis that arg-13 encodes a mitochondrial basic amino acid carrier whose existence was predicted based upon previous physiological, nutritional and biochemical data.
 ...
PMID:Isolation and analysis of the arg-13 gene of Neurospora crassa. 880 90

A cluster of citrulline biosynthetic genes has been cloned and sequenced from a fragment of Lactobacillus plantarum CCM 1904 (ATCC 8014) DNA isolated as complementing a Bacillus subtilis argF mutation. The gene order was carA-argCJBDF, with carA transcribed divergently from the arg cluster. Although other gram-positive bacteria show similar arg clusters, this arrangement for carA is thus far unprecedented. Downstream from the arg cluster, two open reading frames (ORF7 and ORF8) having unknown functions were found. Sequence analysis of the end of a 10.5-kb cloned DNA fragment showed that argF was 3.5 kb from the ldhL gene coding for L-(+)-lactate dehydrogenase. A tree representation of amino acid sequence clustering relationships of 31 ornithine carbamoyltransferases (OTCases) from various organisms revealed two prokaryotic groups: one with ArgF of L. plantarum and one with ArgF of B. subtilis, which are paralogous. This divergence was not observed in vivo because an L. plantarum argF mutant (AM 1215) harboring no OTCase activity was complemented by the argF genes of L. plantarum and B. subtilis. No OTCase activity was detectable when L. plantarum was grown in the presence of saturating amounts of arginine or citrulline. Arginine may repress the citrulline biosynthetic genes in L. plantarum by using 11 identified DNA motifs which resemble the Escherichia coli ARG box consensus and which are in most cases separated by multiples of 11 bp, corresponding to a DNA helical turn. The carA and argCJBDF genes are divergently transcribed. Their putative promoters are 6 bp apart and are partially overlapped by putative ARG boxes, suggesting concerted transcription regulation.
 ...
PMID:Arginine biosynthesis and regulation in Lactobacillus plantarum: the carA gene and the argCJBDF cluster are divergently transcribed. 909 69

In contrast to BALB/c mouse macrophages, the A/J macrophages after activation by interferon gamma (IFN gamma) develop an anti-MHV3 effect which correlates with the resistance to virus infection. To understand the cellular basis of this antiviral effect, we studied the possible involvement of arginine metabolism through nitric oxide (NO) and arginase induction, since these metabolic pathways have been described as implicated in antiviral activities of macrophages. The studies were performed by activating macrophages with inducers of NO (IFN gamma) and arginase (IL4 IL10). NO synthase (iNOS) and arginase inhibitors (N-methyl-arginine, NMA, and hydroxyarginine, OH-ARG) were used. The results show that in both macrophage populations, no spontaneous synthesis of NO occurred and the MHV3 enhanced the NO release induced by IFN gamma. After activation with IFN gamma, BALB/c macrophages released higher amounts of NO than the A/J macrophages. The inhibition of IFN gamma-induced NO-synthesis with NMA or with arginine free medium did not affect the virus replication. In BALB/c macrophages, IL4 or IL10, induced higher amounts of arginase than in A/J macrophages. In both macrophage populations the MHV3 infection had no influence on the arginase synthesized, and the inhibition of the arginase with OH-ARG had no influence on the virus growth. The level of MHV3 replication or inhibition was also not influenced when we used macrophages from knockout mice for the iNOS gene, and as a consequence were unable of synthesizing NO. These data indicate that NO and arginase do not participate in the anti-MHV3 state induced by IFN gamma in macrophages.
 ...
PMID:Anti-MHV3 state induced by IFN gamma in macrophages is not related to arginine metabolism. 941 8

We investigated the mechanism of action of gemfibrozil on high-density lipoproteins (HDL) and apolipoprotein (apo) A-I metabolism and atherogenesis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia and HDL deficiency. Two-month-old WHHL rabbits were fed either a normal control diet or a diet containing 0.5% gemfibrozil for 12 months. In vivo apo A-I kinetics, the fractional rate of cholesterol esterification in HDL (FER[HDL]), which reflects the reactivity of HDL to lecithin:cholesterol acyltransferase, and a morphometrical analysis of atherosclerotic lesions in the descending thoracic aorta, were examined. At 12 months, the mean levels of serum total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in both groups had decreased to approximately 53%, 57%, and 87% of the initial levels (at 0 month), respectively, which is characteristic of homozygous WHHL rabbits of the physiologic influence of aging, and no differences in the levels of serum LDL-C, HDL-C, and triglycerides were found between the two groups. Rabbits treated with gemfibrozil exhibited a decreased FER(HDL) (38% of the controls, P = 0.039). Gemfibrozil induced a significant increase in the total mass of apo A-I (1.7-fold, P < 0.05) and in the rate of apo A-I synthesis (1.6-fold, P < 0.05). The atherosclerotic intimal area was positively correlated with serum LDL-C (P = 0.02) in both groups, but gemfibrozil did not affect the atherosclerotic intimal area. These results indicate that 12 months of treatment with gemfibrozil did not protect against atherosclerosis despite a significant increase in apo A-I synthesis and enhanced HDL function through FER(HDL). It is possible that both the qualitative and quantitative improvement in HDL by gemfibrozil cannot overcome the massive and long-term exposure of the vascular wall to LDL in these animals.
 ...
PMID:Mechanism of action of gemfibrozil on HDL metabolism and atherosclerosis in WHHL rabbits. 949 5


1 2 3 4 5 6 7 8 Next >>