Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two recently identified isozymes of neuraminidase in rat liver were examined for transmission patterns and linkage relationships, and for variation among inbred strains. The isozymes, designated neuraminidase-1 (NEU-1) and neuraminidase-2 (NEU-2), exhibited no electrophoretic mobility variants among the 22 inbred strains examined, but did possess striking interstrain variation in activity phenotypes on electrophoretic gels. The results of a backcross analysis involving the KGH and ACP strains revealed that NEU-1 and NEU-2 phenotypes are independently controlled, each by a single autosomal locus with additively acting alleles. The two loci are unlinked to one another, but the gene controlling NEU-1 is tightly linked to RT1, the rat major histocompatibility complex. This gene is almost certainly identical to Neu-1, a gene identified previously through its effect on "total" activity levels of liver neuraminidase as determined by fluorometric assay of tissue homogenates. NEU-2 and the gene controlling its phenotype were not detected by the fluorometric technique. We designate the genes controlling the NEU-1 and NEU-2 phenotypes as Neu-1 and Neu-2, respectively. Data from this and other studies place Neu-1 between Glo-1 and dw-3. The location of Neu-2 is unknown.
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PMID:Genetic analysis of liver neuraminidase isozymes in Rattus norvegicus: independent control of NEU-1 and NEU-2 phenotypes. 377 Apr 67

The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.
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PMID:Activation of T lymphocytes results in an increase in H-2-encoded neuraminidase. 387 51

The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1b allele. Mouse strains in which meprin activity levels are normal are designated Mep-1a. Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1a F1 hybrids [C3H.A (KkDd) X C3H.OH (KdDk)] were backcrossed with Mep-1b C3H.OH (KdDk) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.
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PMID:Proximity of the Mep-1 gene to H-2D on chromosome 17 in mice. 407 50

Meprin, a glycoprotein with potent metalloendopeptidase activity, is an integral component of the brush border membrane of mouse kidney. Previously we reported that genealogically related inbred mouse strains (C3H and CBA) are markedly deficient in the activity of this enzyme. We report here that meprin deficiency is inherited as an autosomal recessive trait and that several other inbred strains also express low levels of meprin activity. All of the inbred strains deficient in meprin activity are of the H-2k haplotype; however, two strains of this haplotype (C58 and C57BR/cd) expressed normal levels of the proteinase. Congeneic and recombinant mouse strains were examined to determine whether the deficiency was linked to the H-2 complex. The gene controlling the activity of meprin (Mep-1) maps on chromosome 17 to the right of the D end of the major histocompatibility complex. The Mep-1 gene is closely linked to a gene that controls isoenzyme patterns of phosphoglycerate kinase (Pgk-2). This work represents the localization of a gene that determines the activity of an integral cellular endopeptidase in mammalian tissues. In addition, the Mep-1 gene is the only identified gene linked to the major histocompatibility complex that regulates a proteinase activity.
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PMID:Mep-1 gene controlling a kidney metalloendopeptidase is linked to the major histocompatibility complex in mice. 638 65

The low activity of liver neuraminidase that is characteristic of mouse strain SM/J is inherited as a single gene on chromosome 17, near the major histocompatibility complex. This gene, neuraminidase-1 (Neu-1), is represented by the low activity allele Neu-1s in SM/J and the high activity allele Neu-1b in C57BL/6J and most other strains. Previously described variations in the posttranslational processing of acid phosphatase, alpha-mannosidase, arylsulfatase-B, and alpha-glucosidase are attributed to pleiotropic effects of this gene.
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PMID:Gene for neuraminidase activity on mouse chromosome 17 near h-2: pleiotropic effects on multiple hydrolases. 720 20

Mouse fibroblasts do not ordinarily express components for the interleukin-2 receptor (IL-2R alpha, beta, and gamma). An analysis of these cells by reverse transcription followed by polymerase chain reaction, however, indicates the presence of transcripts specific for the IL-2R beta and gamma genes. Transfection of the cDNA for the alpha chain of the human IL-2R into LTK- mouse fibroblast cell line (L3 cells) leads, in long-term cultures, to the formation of transcripts of endogenous mouse IL-2, IL-2R alpha and beta genes, as detected by Northern blotting. Based upon the results of the binding of 125I-labeled IL-2 to the transfected cells, three IL-2-binding proteins of 55 kDa, 65 kDa and 75 kDa were expressed by the transfected cells. The 65-kDa and 75-kDa proteins bound IL-2 in the presence of monoclonal antibodies for the IL-2R alpha chain. These polypeptides assembled to form high-affinity IL-2R, as shown by Scatchard binding analyses. The receptors were functionally active, since the expression of H-2k major histocompatibility complex antigens on the surface membranes of L3 cells was enhanced by exposing the cells to IL-2. Activation of the IL-2 gene was also observed in long-term cultures of L alpha beta cells, another LTK- transfectant expressing the human IL-2R alpha chain. This type of gene activation was not observed in LTK- fibroblasts transfected with cDNA for human IL-2 or IL-2R beta genes. In L3 and L alpha beta cells, transcription of the endogenous IL-2 gene was suppressed by cyclosporin A and enhanced by cycloheximide. These data may have implications for gene therapy of cancer cells.
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PMID:Non random activation of endogenous interleukin-2, (IL-2), IL-2 receptor alpha and IL-2 receptor beta genes after transfection of mouse fibroblasts with a cDNA for the alpha chain of the human IL-2 receptor. 762 67

Meprins, membrane-bound oligomeric metalloendopeptidases, contain alpha and/or beta subunits. Their activities have been found in the mouse and rat kidney. The cloned cDNA for the mouse alpha subunit of meprin A (EC cloned cDNA for the mouse alpha subunit of meprin A (EC 3.4.24.18) was used here to survey mRNA expression in kidney of different mouse strains and in various tissues of mice and rats. A single message of 3.6 kilobases was found in kidney of random bred (ICR) and inbred mice (C57BL/6, DBA/2) that contain high meprin A activity and in Sprague-Dawley rat kidney. The alpha subunit message was undetectable in the kidney of C3H/He and CBA mice, inbred strains that do not express meprin A activity. Therefore, meprin A activity in the kidney of mouse strains correlates with the amount of alpha subunit mRNA present. The 3.6-kilobase mRNA meprin alpha subunit message was also detected in the small intestine of the rat but not in mice. No message was detected in brain, heart, skeletal muscle, liver, lung, or spleen of mice or rats. Polymerase chain reaction amplification or Southern blot analysis of genomic DNA revealed that the gene for the alpha subunit is present in all mouse strains as well as in human, monkey, rat, mouse, dog, cow, rabbit, and chicken, but it was not detected in yeast. There is one gene copy present in the mouse genome. The gene was localized to mouse chromosome 17 centromeric to the major histocompatibility complex (H-2) by the interspecific backcrossing method. The localization of this allele to Mep-1, the gene previously found to regulate the expression of meprin A activity in mice, supports the proposal that Mep-1 is the structural gene for the alpha subunit.
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PMID:Tissue-specific expression and chromosomal localization of the alpha subunit of mouse meprin A. 768 77

Zinc is known to be greatly involved in the regulation of immune functions. Pharmacological zinc supplementation, leading to serum zinc concentrations of more than 0.025 mM, has often been suggested to improve immune responses. However, the exact influence of elevated zinc level on immune functions has not yet been investigated. We found that zinc level selectively enhances cytokine induction by lipopolysaccharide (LPS) in a concentration-dependent fashion: as little as 0.0125 mM supplemental zinc led to nearly 50% elevated interleukin-1 beta (IL-1 beta) levels both in polymorphonuclear cells (PBMC) and whole-blood cultures. The secretion of interferon-gamma (IFN-gamma) could be increased more than 10-fold by 0.1 mM zinc. This could not be observed during stimulation with phytohaemagglutin (PHA). In contrast, zinc levels concentration-dependently down-regulated monocyte activation caused by the superantigens, staphylococcal enterotoxins A and E (SEA, SEE, more than 90% down-regulation by 0.1 mM zinc), the Mycoplasma arthritidis-derived superantigen (MAS), but not toxic shock syndrome toxin-1 (TSST-1), while T-cell response remained unaffected. This was not the result of chemical degradation of the superantigens. We assume that zinc concentration regulates interactions between SEA, SEE and MAS, but not TSST-1 and their major histocompatibility complex (MHC) class II-binding sites. Our data demonstrate that zinc levels control the secretion of IFN-gamma and monokines after both LPS and superantigen challenge within a clinically relevant range of concentrations. This reveals new perspectives and indications for zinc supplementation and also indicates potential risks of therapeutic application of zinc.
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PMID:Zinc regulates cytokine induction by superantigens and lipopolysaccharide. 775 Oct 4

Experimental approaches which exploit the targeted cytolytic activity of lymphocytes are being developed for cancer therapy. We generated cytotoxic T lymphocytes (CTLs) with specificity for ERBB2 receptor-expressing tumor cells. A binding function was conferred directly on the zeta chain of the T-cell receptor (TCR) complex to circumvent major histocompatibility complex-restricted antigen recognition through the alpha and beta chains of the TCR. A chimeric gene was constructed which encoded a single-chain Fv antibody (scFv, consisting of the joined heavy- and light-chain variable domains of a monoclonal antibody against the extracellular domain of the ERBB2 receptor), a hinge region as a spacer, and the zeta chain of the TCR. This gene was introduced into CTLs by retroviral gene transfer. The signaling potential of the scFv/hinge/zeta receptors was demonstrated by secretion of interferon gamma upon coincubation with ERBB2-expressing cells. Target cells expressing the ERBB2 gene were lysed in vitro with high specificity by the scFv/hinge/zeta-expressing T cells. The growth of ERBB2-transformed cells in athymic nude mice was retarded by adoptively transferred scFv/hinge/zeta-expressing CTLs. Transduced CTLs labeled with a fluorescent dye were specifically detected in tumor sections. Our results suggest that tumor cell lysis by CTLs grafted in vitro with a major histocompatibility complex-independent recognition could become a gene-therapy approach to cancer treatment.
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PMID:Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells. 791 Apr 5

Macrophages from C2D transgenic mice deficient in the expression of major histocompatibility complex (MHC) class II proteins were used to identify binding sites for superantigens distinct from the MHC class II molecule. Iodinated staphylococcal enterotoxins A and B (SEA and SEB) and exfoliative toxins A and B (ETA and ETB) bound to C2D macrophages in a concentration-dependent and competitive manner. All four toxins increased F-actin concentration within 30 s of their addition to C2D macrophages, indicating that signal transduction occurred in response to toxin in the absence of class II MHC. Furthermore, ETA, ETB, SEA, and, to a lesser extent, SEB induced C2D macrophages to produce interleukin 6. Several molecular species on C2D macrophages with molecular masses of 140, 97, 61, 52, 43, and 37 kDa bound SEA in immunoprecipitation experiments. These data indicate the presence of novel, functionally active toxin binding sites on murine macrophages distinct from MHC class II molecules.
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PMID:Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins. 806 7


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