Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mouse retrovirus containing the c-myc oncogene was found to induce tumors of mononuclear phagocytic cells in vivo. All tumors expressed the c-myc retroviral gene but not the endogenous c-myc gene (with one exception), and virtually all tumors were clonal with a unique proviral integration. This observation, coupled with a lag time in tumor formation, suggests that a second event, in addition to c-myc proviral integration, is necessary for the generation of neoplastic cells in vivo. All of the tumor cells expressed high levels of mRNA for both the putative colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product), as well as the c-fos proto-oncogene. Although all of the tumor cells proliferated in culture without the addition of exogenous CSF-1, which is required for the proliferation of primary macrophages partially transformed by the same c-myc retrovirus, several phenotypes were observed with respect to the expression of CSF-1 and granulocyte-macrophage CSF and to their growth factor responsiveness. The proliferation of one tumor, which secreted high levels of CSF-1, was blocked by specific anti-CSF-1 serum. This tumor was found to express altered CSF-1 mRNA and to have a DNA rearrangement at the CSF-1 locus. In this particular case, the data indicate that a CSF-1 gene rearrangement was the secondary event in development of the tumor. The pleiotropy of phenotypes among the other tumors indicated that there are a variety of other mechanisms for such secondary events which can be investigated with this system.
Mol Cell Biol 1987 Feb
PMID:Induction of clonal monocyte-macrophage tumors in vivo by a mouse c-myc retrovirus: rearrangement of the CSF-1 gene as a secondary transforming event. 354 79

The rate constants of 1H----3H exchange between water and C8H-groups of purine residues of alternating polynucleotides: poly[d(A-C)].poly[d(G-T)] and poly[d(A-T)].poly[d(A-T)], as well as Escherichia coli DNA, dAMP and dGMP, in solutions with high concentration (4.3 or 6 M) CsF, in water ethanol (60%) solution and (in comparison) in 0.15 M NaCl were determined at 25 degrees C. The 1H----3H exchange rate exchange rate constants for adenylic (kA) and guanylic (kG) residues of polynucleotides were compared with the corresponding constant for DNA and mononucleotides. It was shown that at conditions when poly[d(G-T)] and poly[d(A-T)].poly[d(A-T)] exhibit the "X-form" CD spectrum, alteration of exchange rates in polynucleotides (approximately 2-fold increase in kA in CSF and approximately 1.5-fold decrease in kA and kG in 60% ethanol with 0.15 M NaCl) is due to the effect of solvents on the chemical reactivity of purine residues, but does not reflect a conformational transition. The analysis of these results allows us to conclude, that alternating polynucleotides under the above mentioned conditions retain roughly the conformations inherent in them in 0.15 M NaCl: poly[d(A-C)].poly[d(G-T)] conformation in 4.3 m CsF or 60% ethanol differs only insignificantly from the "canonic" B-DNA, whereas the poly[d(A-T)].poly[d(A-T)] conformation in 6 M CSF corresponds to B-alternating DNA.
Mol Biol (Mosk)
PMID:[Study of conformation characteristics of "X-form" of alternating polynucleotides by the method of slow 1H----3H transition]. 368 78

Double labeling studies of the pattern of protein synthesis in goldfish and mouse brain identified a class of glycoproteins (the ependymins) whose turnover rate was enhanced after training. A variety of control experiments indicated that these macromolecules have an important role in the molecular and cell biology of learning. Antisera to the ependymins when injected into the brains of trained goldfish cause amnesia of a newly acquired behavior. Isolation and localization studies by immunocytochemical methods indicate that the ependymins are released into the brain extracellular fluid by a class of neurosecretory cells. In mammalian brain ependymin-containing cells are highly concentrated in the limibic system. The ependymins are constituted from two disulfide-linked acidic polypeptide chains (M.W.37K and 31K). They contain at least 5% covalently bound carbohydrate per chain with mannose, galactose, N-acetylglucosamine and N-acetylneuraminic acid as the predominant components. The highly soluble ependymins can rapidly polymerize to form an insoluble fibrous matrix if calcium is removed from solution by the addition of a Ca2+-chelating agent or dialysis. The self-aggregation property of the ependymins can be triggered by the depletion of Ca2+ from the extracellular space. Studies of the kinetics of the aggregation phenomenon by measurements of turbidity changes indicate that the process can be terminated but not reversed by restoring Ca2+ to its normal CSF level. Immunohistochemical studies of the brains of trained goldfish show the presence of punctate statining sites in the perimeter of certain cells located in specific brain regions. This suggests that ependymin aggregation might occur in vivo during learning. A molecular hypothesis relating the aggregation properties of the ependymins to neuroplasticity and learning is proposed.
Cell Mol Neurobiol 1985 Jun
PMID:The role of brain extracellular proteins in neuroplasticity and learning. 402 66

A polymerase chain reaction (PCR) assay based on the penicillin-binding protein gene PBP2B identified the presence of DNA specific for Streptococcus pneumoniae in the serum and CSF of a patient with culture-proven bacteremia and meningitis. Positive signals were seen to dilutions of 1:125 and 1:390,625 for the blood and CSF specimens, respectively. Potential advantages of PCR over conventional culture include exquisite sensitivity, faster results and the ability to identify the organisms by the presence of species-specific DNA even in patients pretreated with antibiotics.
Mol Cell Probes 1995 Jun
PMID:Identification of a patient with Streptococcus pneumoniae bacteremia and meningitis by the polymerase chain reaction (PCR). 747 7

The crystal structures of recombinant canine and bovine granulocyte colony stimulating factor (G-CSF) have been determined by X-ray crystallography, using molecular replacement with recombinant human G-CSF as a model. G-CSF is a member of the cytokine family of glycoproteins that stimulate the differentiation and proliferation of blood cells. Human, bovine and canine G-CSF all have a molecular mass of about 19 kDa and share an amino acid sequence identity of about 80%. Two crystal forms of canine G-CSF have been solved. Form I recombinant canine G-CSF (rcG-CSFI; space group C2) contains one molecule in the asymmetric unit while form II canine G-CSF (rcG-CSFII; space group P2(1)) has two molecules in the asymmetric unit and bovine G-CSF (rbG-CSF; space group P2(1)2(1)2(1)) contains one molecule in the asymmetric unit. rcG-CSFI has been refined to an R factor of 20.7% with data to 2.3 A resolution and rcG-CSFII has been refined to an R factor of 19.3% with data to 2.2 A resolution. rbG-CSF has been refined to an R factor of 21.3% with data to 1.7 A resolution. The structure of human, canine and bovine G-CSF is an antiparallel 4-alpha-helical bundle with up-up-down-down connectivity. With the exception of one highly exposed loop (residues 66 to 74), the human, canine and bovine structures are very similar to each other. Using our series of G-CSF crystal structures we developed a function that describes the probability that a particular residue position (i) contributes to a G-CSF receptor binding site based on two principles, (1) high sequence conservation in the primary sequence of human, bovine, canine and murine G-CSF and (2) conservation of high solvent accessibility in the human, bovine and canine crystal structures. On the basis of this probability function as well as a comparison of G-CSF to the crystal structure of human growth hormone (hGH) complexed with the extracellular domain of the human growth hormone receptor (hGHbp), residues that contribute to potential G-CSF receptor binding sites are identified.
J Mol Biol 1993 Dec 05
PMID:Crystal structure of canine and bovine granulocyte-colony stimulating factor (G-CSF). 750 36

Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF) stimulated the differentiation of murine myeloblasts and promyelocytes to mature neutrophils. In connection with this, myeloperoxidase activity of these progenitor cells was decreased by either histamine or rG-CSF treatment. After pretreatment with histamine at 1 microM, both differentiation and the decrease in myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the number of rG-CSF binding sites on the surface of neutrophil progenitor cells increased after histamine treatment. The histamine-induced increase in rG-CSF binding appeared to be definitely through H2 receptors. Furthermore, the increase in rG-CSF binding sites due to histamine treatment seemed to take place in association with the externalization of G-CSF receptors, because 1) the binding increase was observed in the presence of cycloheximide, 2) no concomitant increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D effectively prevented the increase in rG-CSF binding due to histamine. In neutrophil progenitors, cAMP contents increased very rapidly and significantly after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG-CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However, when progenitor cells were pretreated with protein kinase A inhibitors, the histamine-induced increase in rG-CSF binding was remarkably decreased. This result seems to indicate that the stimulatory effects of histamine on rG-CSF binding to progenitor cells are intimately related to the cAMP-protein kinase A system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil progenitors was markedly reduced by either histamine or rG-CSF treatment. It was concluded that rG-CSF-induced differentiation of murine neutrophil progenitors was augmented by histamine pretreatment mainly due to an increase in rG-CSF receptors on these cells and this increase might be related to the externalization of rG-CSF receptors.
Mol Pharmacol 1994 May
PMID:Reinforcement effect of histamine on the differentiation of murine myeloblasts and promyelocytes: externalization of granulocyte colony-stimulating factor receptors induced by histamine. 751 13

The secondary structure and backbone dynamics of the cytokine, human granulocyte colony-stimulating factor (hG-CSF) have been determined by heteronuclear nuclear magnetic resonance (NMR) techniques. Virtually complete NH, C alpha H, C beta H 15N, 13C alpha, and 13C beta assignment of the 175-residue recombinant protein, methionyl-[Cys-17-Ser]-hG-CSF, was achieved by use of three-dimensional (3D) heteronuclear 1H-15N and triple-resonance 1H-15N-13C experiments. Spectra recorded at 750 MHz aided the assignment of severely overlapped regions. The structures of G-CSF from several species have recently been determined by X-ray diffraction [Hill, C. P., Osslund, T. D., & Eisenberg, D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 5167-5171; Lovejoy, B., Cascio, D., & Eisenberg, D. (1993) J. Mol. Biol. 234, 640-653]. Like several cytokines, hG-CSF has a four-helix topology (A-D) with overhand loop connections, but with an additional helical segment (A') identified in the connection between helix A and helix B. The solution-state determination of the secondary structure is based on short- and medium-range NOEs, backbone J-couplings, and NH exchange data and is corroborated by 13C alpha secondary shifts. The helices are defined as follows: A, 10-38; A',44-53; B, 71-91; C, 102-123; D, 143-172. The dynamics of the amide backbone resonances, investigated using 1H-15N heteronuclear NMR, indicate a rigid protein core with some increased mobility in the AB loop and more pronounced mobility in the CD loop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary structure and backbone dynamics of human granulocyte colony-stimulating factor in solution. 751 82

Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix glycoproteins participating in tissue morphogenesis and repair. The regulation of their synthesis and deposition during airway inflammation and their possible contribution in asthma are poorly understood. In this study, modulation of Fn and Tn production was investigated in transformed human bronchial epithelial cells in culture. The cells were treated with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), a combination of these cytokines, interleukins 3 and 6 (IL-3 and IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), and a combination of IL-3 and IL-6 for 48 h. Immunofluorescence and immunoblotting methods with monoclonal antibodies to Fn and Tn antibodies suggested the production of some Fn and Tn in the untreated cells. Fn was minimally induced in response to IFN-gamma and TNF-alpha, when compared with the untreated cells, whereas TNF-alpha and especially the IFN-gamma plus TNF-alpha combination resulted in a prominent Tn induction. Interleukins and GM-CSF did not induce Fn or Tn in any case. These results show that human bronchial epithelial cells are capable of producing Fn and Tn. The modulation of Fn and Tn may have an important impact on the pathology of epithelial cells during airway inflammation in vivo.
Am J Respir Cell Mol Biol 1995 Jul
PMID:Modulation of fibronectin and tenascin production in human bronchial epithelial cells by inflammatory cytokines in vitro. 754 Dec 19

Granulocyte-macrophage colony-stimulating factor (GM-CSF) mainly stimulates proliferation and maturation of myeloid progenitor cells. Although the signal transduction pathways triggered by GM-CSF receptor (GMR) have been extensively characterized, the roles of GMR signals in differentiation have remained to be elucidated. To examine the relationship between receptor expression and differentiation of hemopoietic cells, we used transgenic mice (Tg-mice) that constitutively express human (h) GMR at almost all stages of hemopoietic cell development. Proliferation and differentiation of hemopoietic progenitors in bone marrow cells from these Tg-mice were analyzed by methylcellulose colony formation assay. High affinity GMR interacts with GM-CSF in a species-specific manner, therefore one can analyze the effects of hGMR signals on differentiation of mouse hemopoietic progenitors using hGM-CSF. Although mouse (m) GM-CSF yielded only GM colonies, hGM-CSF supported various types of colonies including GM, eosinophil, mast cell, erythrocyte, megakaryocyte, blast cell, and mixed hemopoietic colonies. Thus, the effects of hGM-CSF on colony formation more closely resembled mIL-3 than those of mGM-CSF. In addition, hGM-CSF generated a much larger number of blast cell colonies and mixed cell colonies than did mIL-3. hGM-CSF also generated erythrocyte colonies in the absence of erythropoietin. Therefore, GM-CSF apparently has the capacity to promote growth of cells of almost all hemopoietic cell lineages, if functional hGMR is present.
Mol Biol Cell 1995 May
PMID:A human GM-CSF receptor expressed in transgenic mice stimulates proliferation and differentiation of hemopoietic progenitors to all lineages in response to human GM-CSF. 754 29

The presentation and recognition of foreign antigen is the critical initial event in the development of local immunity. In the lung, antigen-presenting cell activity is largely attributable to pulmonary dendritic cells (DC) that are distributed along the airways and throughout the pulmonary interstitium in close proximity to overlying alveolar epithelial cells. To test the hypothesis that DC immunostimulatory activity might be locally regulated by overlying alveolar epithelial cells, we evaluated the ability of rat type II alveolar epithelial cells to influence the capacity of purified rat pulmonary DC to stimulate T-cell proliferation in an allogeneic, mixed leukocyte reaction. We found that alveolar epithelial cells greatly enhanced the ability of dendritic cells to induce T-cell proliferation. This effect on DC immunostimulatory activity was mediated by a soluble factor preferentially secreted from the basolateral epithelial cell surface. Alveolar epithelial cultures were found to express mRNA for granulocyte macrophage colony-stimulating factor (GM-CSF), and blocking antibodies against GM-CSF partially neutralized the effect of epithelial cell-conditioned media on DC stimulatory activity, indicating that the effect was due at least in part to alveolar epithelial cell-derived GM-CSF. Through the polar secretion of GM-CSF, alveolar epithelial cells may play an important role in creating distinct immunologic environments within the lung.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Regulation of rat pulmonary dendritic cell immunostimulatory activity by alveolar epithelial cell-derived granulocyte macrophage colony-stimulating factor. 754 72


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