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

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiation hybrid mapping was used in conjunction with a natural deletion mapping panel to predict the order of and distance between 13 loci in the distal portion of the long arm of human chromosome 5. A panel of irradiation hybrids containing fragments of 5q was generated from an HPRT+ Chinese hamster-human cell hybrid containing a derivative chromosome 5 [der(5)t(4;5)(5qter----5p15.1::4p15.1----4pter)] as its only human DNA. One hundred nine radiation hybrids containing human DNA were screened with polymerase chain reaction primer sets representing nine genes encoding growth factors, growth factor receptors, or hormone receptors (IL3, IL4, IL5, CSF1R, FGFA, ADRB2, GRL, GABRA1, and DRD1) as well as four other loci (FER, SPARC, RPS14, and CD14) to generate a radiation hybrid map of the area 5q21-q35. A physical map predicting the order of and distance between the 13 loci was constructed based on segregation of the 13 loci in hybrid clones. The radiation hybrid panel will be useful as a mapping tool for determining the location and order of other genes and polymorphic loci in this region as well as for generating new DNA probes from specific regions.
...
PMID:Radiation hybrid map of 13 loci on the long arm of chromosome 5. 166 88

A double-blind placebo-controlled trial of allergen injection immunotherapy in adult patients with severe summer hayfever. We used a partially purified biologically standardised grass pollen depot preparation (Alutard SQ, ALK Denmark Ltd.). Immunotherapy was extremely effective in reducing symptoms and medication requirements. Clinical improvement was accompanied by a decrease in both a target organ (conjunctival) and skin sensitivity. The injections were well-tolerated with minimal side effects. The results suggest that 30 minutes rather than 2 hours is an acceptable post-injection observation period. Successful immunotherapy was accompanied by suppression of the late cutaneous response to allergen. Specific immunostaining of skin biopsies revealed inhibition of the characteristic CD4+ T cell and EG2+ activated eosinophil cellular infiltrate during the late response. There was a significant relationship between CD4+ T cell and eosinophil counts after immunotherapy, i.e. the lower the number of infiltrating CD4+ cells, the lower the eosinophil counts. An unexpected finding was a prominent CD25+ (interleukin-2 receptor positive) cellular infiltrate which was only observed following Alutard SQ. Further studies involving double immunostaining methods should identify the phenotype of these activated, IL-2R+ cells. Based on murine studies Mosmann and colleagues have classified T cell responses into two types according to their profile of lymphokine production [11]. TH1 cells produce predominantly the IL-4 family of cytokines (IL-3, IL-4, IL-5) whereas TH2 cells produce predominantly interleukin-2 and interferon gamma. Insofar as the Mosmann classification may possibly be relevant to human T cell responses, the above findings would support a switch from a "TH2-" to a "TH1-" lymphocyte response following immunotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Immunotherapy and allergic inflammation. 203 47

Using (a) somatic cell hybrids retaining partial chromosome 5 and (b) clinical samples from patients with acquired deletions of the long arm of chromosome 5, combined with chromosome 5-linked DNA probes, some of which exhibited RFLPs, we have determined the order of a series of genes on chromosome 5. The order established is 5pter----MLVI-2----cen----HEXB----DHFR----Pi227- --- cp12.6----(IL5,IL4)----IL3----GMCSF---- FGFA---- (CSF1R,PDGFR)----(treC,ADRBR)----(ARH-H9,CSF1 )----qter. The suggested order and orientation for the closely linked IL3/GMCSF gene pair is cen----5' IL3 3'----5' GMCSF 3'----qter, on the basis of analysis of the GMCSF rearrangement in HL60 DNA. The map position of the GRL locus, which was consistent with both somatic cell hybrid and 5q- analyses, was telomeric to GMCSF and centromeric to CSF1R/PDGFR, near FGFA. Long-range restriction-enzyme analysis of 5q- DNAs did not detect rearrangements of 5q-linked probes except in HL60 DNA, but it did reveal putative long-range RFLPs of several loci. RFLPs for GRL, Pi227, cp12.6, IL3, and CSF1R can detect deletions in bone marrow and in leukemia cells from patients with acquired 5q deletions.
...
PMID:Order of genes on human chromosome 5q with respect to 5q interstitial deletions. 229 53

Receptors for insulin, low-density lipoprotein, and colony stimulating factor 1 are associated with diabetes, atherosclerosis, and cancer in man. Complementary DNA clones for Insr, Ldlr, and Csfmr were used to chromosomally assign the three genes in mouse. In contrast to their close linkage on the short arm of human Chromosome 19, Insr and Ldlr are asyntenic, residing on mouse Chromosomes 8 and 9, respectively. The genes for CSF1R, CSF1, CSF2, IL-3, and IL-5 form a cluster on the long arm of human Chromosome 5. In mouse, Csfm, Csfgm, and IL-3 are syntenic on Chromosome 11. The Csfmr gene was assigned to mouse Chromosome 18 and is thus unlinked to other members of this gene cluster. These gene assignments provide additional topographical information on conservation of linkage groups in man and mouse and provide a genetic framework for evaluating the possible roles for the three receptor genes in genetic diseases in mouse.
...
PMID:Chromosome assignment of mouse insulin, colony stimulating factor 1, and low-density lipoprotein receptors. 306 42

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
...
PMID:Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. 750 78

Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus strains secreting exotoxins such as the staphylococcal enterotoxin B (SEB) and A (SEA). Nonetheless the role of SEB and SEA in AD is yet unknown. We analyzed the responsiveness of peripheral blood mononuclear cells (PBMCs) and isolated T cells from donors with AD and from normal donors to SEB and SEA. PBMCs as well as T cells from normal donors showed a significantly enhanced proliferation after stimulation with enterotoxin B, whereas the 3H-thymidine uptake of the T lymphocytes from patients with AD was markedly suppressed. Furthermore, we show that IFN-gamma mRNA and protein and mRNA for both chains of IL-12 (p35 and p40) are produced in human PBMCs from normal donors upon stimulation with SEB and SEA. In contrast to normal donors T cells from donors with AD predominantly express mRNA for IL-4, IL-5, and only diminished levels for IFN-gamma and IL-12 upon stimulation with SEB and SEA. Furthermore, in contrast to normal donors, PBMCs from donors with AD spontaneously produce high levels of IgE and express increased levels of CD23, the low-affinity receptor for IgE. Nonetheless, the superantigens by themselves, from 0.1 fg up to 1 microgram/10(6) cells, induced neither IgE secretion nor CD23 expression on PBMCs. Moreover, the addition of superantigens to IL-4-treated PBMC cultures diminished or totally suppressed the IL-4-induced IgE synthesis and CD23 expression. No differences were observed between PBMCs from normal donors of donors with AD. Both PBMCs isolated from normal and atopic donors produced high levels of soluble IL-4-receptor (up to 210 +/- 90 pg/ml). Addition of soluble IL-4-receptor to PBMC cultures downregulated the IL-4-induced IgE synthesis and CD23 expression in unstimulated as well as in SEB-stimulated PBMCs from normal donors and donors with AD. Our results suggest that superantigen-producing staphylococcal strains on the skin of patients with AD may modulate and/or amplify allergic inflammation.
...
PMID:Responsiveness of peripheral blood mononuclear cells from normal and atopic donors to microbial superantigens. 781 40

Two subsets of differentiated murine helper T cells, Th1 and Th2, based on secretion products in response to antigen have been described (Cher & Mosmann 1987, Coffman et al. 1988, Lopez et al. 1988, Paliard et al. 1988, Patel et al. 1988, Mosmann & Coffman 1989). To analyse immunological function of antigen-specific CD4+T cells in human schistosomiasis, we produced schistosomal egg antigen-specific T cell clones from a former patient. We identified four different types of CD4+ T cell clones by analysis of cytokine production. Two of the four types of the clones corresponded to murine Th1 or Th2 subsets; a third type was of the Th0 subset (Th1 + 2) and a fourth type produced IL-5 dissociated from IL-4. Analysis of the antigen(s) recognized by these T cell clones showed that all of the clones proliferated in response to soluble egg antigen(s) (SEA) found within a pl fraction whose pH was 5.2. T cell Western blot analysis of the stimulatory pl fraction demonstrated that the apparent Mr of the relevant antigens recognized by the clones were 38 kDa for the Th2 homologue, and 45-55 kDa for the Th1 homologue.
...
PMID:Heterogeneity of antigen-specific CD4+ T cell clones from a patient with Schistosomiasis mansoni. 786 62

The q23-q33 region of human chromosome 5 encodes a large number of growth factors, growth factor receptors, and hormone/neurotransmitter receptors. This is also the general region into which several disease genes have been mapped, including diastrophic dysplasia, Treacher Collins syndrome, hereditary startle disease, the myeloid disorders that are associated with the 5q-syndrome, autosomal-dominant forms of hereditary deafness, and limb girdle muscular dystrophy. We have developed a framework physical map of this region using cosmid clones isolated from the Los Alamos arrayed chromosome 5-specific library. Entry points into this library included 14 probes to genes within this interval and one anonymous polymorphic marker locus. A physical map has been constructed using fluorescence in situ hybridization of these cosmids on metaphase and interphase chromosomes, and this is in good agreement with the radiation hybrid map of the region. The derived order of loci across the region is cen-IL4-IL5-IRF1-IL3-IL9-EGR1-CD1 4-FGFA-GRL-D5S207-ADRB2-SPARC-RPS14+ ++-CSF1R- ADRA1, and the total distance spanned by these loci is approximately 15 Mb. The framework map, genomic clones, and contig expansion within 5q23-q33 should provide valuable resources for the eventual isolation of the clinically relevant loci that reside in this region.
...
PMID:A physical map of 15 loci on human chromosome 5q23-q33 by two-color fluorescence in situ hybridization. 832 47

Interleukin-5 (IL-5) is one of the major regulators of eosinophilic granulocytes in vivo. IL-5 exerts its pleiotropic effects by binding to the IL-5 receptor, which is composed of an IL-5-specific alpha chain and a common betac chain shared with the receptors for IL-3 and granulocyte-macrophage colony-stimulating factor. Previous studies have shown that binding of IL-5 to its receptor triggers the activation of multiple signaling cascades, including the Ras/mitogen-activated protein kinase, the phosphatidyl -3'-kinase, and the Janus kinase/signal transducer and activator of transcription pathways. Here we describe that IL-5 activates the serine/threonine protein kinase Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway. We show that IL-5 activates TPA response element (TRE)-dependent transcription in transfection experiments. TRE activation by IL-5 is mediated by a region of the betac (577-581) that is also responsible for activation of JNK/SAPK and for activation of dyad symmetry element (DSE)-dependent transcription. Dominant-negative SAPK or ERK kinase-1 was used to demonstrate that JNK/SAPK activation is necessary for induction of DSE- and TRE-dependent transcription by IL-5, whereas extracellular signal-regulated kinase 2 was not essential for TRE- and DSE-dependent transcription. By contrast, IL-5-induced activation of the tyrosine kinase Janus kinase 2 seems to be a prerequisite for TRE- and DSE-dependent transcription. Taken together, we show for the first time that IL-5 activates kinases of the JNK/SAPK family, and that this activation is linked to IL-5-induced TRE- and DSE-dependent transcription.
...
PMID:Activation of 12-O-tetradecanoylphorbol-13-acetate response element- and dyad symmetry element-dependent transcription by interleukin-5 is mediated by Jun N-terminal kinase/stress-activated protein kinase kinases. 899 40

Activation and recruitment of eosinophils in allergic inflammation is in part mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However, little is known concerning the signal transduction mechanisms by which this activation occurs. We have investigated tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the p21ras-ERK signaling pathway in human eosinophils. The related cytokines interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine-associated PI3K activity. Protein kinase B (PKB) is a downstream target of PI3K activation by growth factors. Induction of PKB phosphorylation in human eosinophils was transiently induced on activation with the cytokines IL-4 and IL-5, as well as the chemoattractants PAF, C5a, and RANTES showing a broad activation profile. Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44(ERK1) and p42(ERK2), showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF. Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5 and PAF-primed eosinophils. In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions.
...
PMID:Analysis of signal transduction pathways in human eosinophils activated by chemoattractants and the T-helper 2-derived cytokines interleukin-4 and interleukin-5. 951 56


1 2 3 4 5 6 7 8 9 10 Next >>

---