共查询到20条相似文献,搜索用时 31 毫秒
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A differentiation-associated 93-kDa tyrosine kinase (p93) was purified previously from the human promyelocytic leukemia cell line HL-60. The present study conclusively identifies p93 as the c-fes proto-oncogene product and shows that expression of p93c-fes and its associated tyrosine kinase activity are marked in mature granulocytes, monocytes, and human myeloid leukemia cell lines. Antisera to peptides obtained by expression of c-fes cDNA fragments in Escherichia coli reacted strongly with p93 purified from HL-60 cells. Western blots using one of these antisera demonstrated high levels of p93c-fes protein in normal human granulocytes and monocytes, as well as the cell lines KG-1, THP-1, HEL, and U-937, all of which can be induced to differentiate along the myelomonocytic pathway. Conversely, in cell lines resistant to myeloid differentiation, p93c-fes expression was either very low or absent. Expression of immunoreactive p93c-fes in these cell lines showed a strong positive correlation with p93c-fes tyrosine kinase activity, which was measured in cell extracts using a nondenaturing gel assay. Finally, the expression of p93c-fes, its tyrosine kinase activity, and the binding of 125I-granulocyte-macrophage colony-stimulating factor (GM-CSF) were all coordinately increased in HL-60 cells treated with the granulocytic differentiation inducer dimethyl sulfoxide, while all three parameters were low in untreated or differentiation-resistant HL-60 cells. These results suggest that expression of p93c-fes tyrosine kinase activity may be an essential component of myeloid differentiation and responsiveness to granulocyte-macrophage colony-stimulating factor. 相似文献
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c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3. 总被引:18,自引:2,他引:16
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Y Hanazono S Chiba K Sasaki H Mano A Miyajima K Arai Y Yazaki H Hirai 《The EMBO journal》1993,12(4):1641-1646
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are hematopoietic growth factors which stimulate the proliferation and differentiation of myeloid progenitor cells. There is a considerable degree of overlap in target cell specificity and the functional effects of GM-CSF and IL-3. GM-CSF and IL-3 induce a nearly identical pattern of protein-tyrosine phosphorylation in certain cell lines, although their receptors have no kinase domains. Furthermore, their receptor complexes share one subunit (designated as beta). These observations raise the possibility that GM-CSF and IL-3 have a common signaling pathway. Here we show that both GM-CSF and IL-3 induce tyrosine phosphorylation and kinase activity of the c-fps/fes proto-oncogene product (p92c-fes), a non-receptor protein-tyrosine kinase, in a human erythro-leukemia cell line, TF-1, which requires GM-CSF or IL-3 for growth. In addition, GM-CSF induces physical association between p92c-fes and the beta chain of the GM-CSF receptor. p92c-fes is therefore a possible signal transducer of several hematopoietic growth factors including GM-CSF and IL-3 through the common beta chain. 相似文献
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Ersvaer E Hampson P Hatfield K Ulvestad E Wendelbo Ø Lord JM Gjertsen BT Bruserud Ø 《Cancer immunology, immunotherapy : CII》2007,56(6):913-925
Cytokines are released during T cell activation, including the potentially anti-leukemic interferon-γ (IFNγ), but also the
hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) that enhance proliferation and inhibit
apoptosis of acute myelogenous leukemia (AML) cells. In the present study we investigated the release of IFNγ and GM-CSF by
circulating T cells in AML patients with chemotherapy-induced cytopenia. T cells were activated with anti-CD3 plus anti-CD28
in a whole-blood assay in the presence of their natural cytokine network. We examined 63 samples derived from 16 AML patients
during 28 chemotherapy cycles. Activated T cells showed a broad cytokine release profile, but IFNγ and GM-CSF levels showed
a significant correlation and were generally higher than the other cytokine levels. Higher IFNγ and GM-CSF responses were
associated with a low CD4:CD8 ratio, older patient age and no ongoing chemotherapy indicating potential utility of T cell
activation regimes for the older AML patient. The cytokine levels could be further increased by the novel protein kinase C
agonist PEP005, which also induced significant production of IL2 and TNFα which could contribute to anti-tumor effects in
AML patients. We conclude that remaining T cells after intensive AML therapy show a broad cytokine release profile including
high and significantly correlated levels of potentially anti-leukemic IFNγ and the AML growth factor GM-CSF. The final outcome
of an AML-initiated T cell cytokine response will thus depend on the functional characteristics of the AML cells, in particular
the relative expression of IFNγ and GM-CSF receptors which differs between AML patients. 相似文献
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Autostimulatory mechanisms in myeloid leukemogenesis 总被引:3,自引:0,他引:3
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J Miyauchi C Wang C A Kelleher G G Wong S C Clark M D Minden E A McCulloch 《Journal of cellular physiology》1988,135(1):55-62
Recombinant hemopoietic colony-stimulating factors (CSFs), including GM-CSF, G-CSF and IL-3, have been shown to be effective stimulators of both self-renewal and terminal differentiation of blast stem cells in acute myeloblastic leukemia (AML). We have examined the activity of a fourth growth factor, recombinant CSF-1 (or M-CSF), on the growth of leukemic blasts in culture. CSF-1 was found to be active on some, but not all, blast populations. In sensitive cells, CSF-1 often stimulated the production of adherent blast cells incapable of division. This observation leads us to suggest that CSF-1 may be useful in the treatment of selected cases of AML. 相似文献
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K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation 总被引:5,自引:0,他引:5
Expression of the proto-oncogene p93c-fes and its associated tyrosine kinase activity is marked in mature granulocytes, monocytes, differentiated HL-60 leukemia cells, and leukemia cell lines KG-1, THP-1, HEL, and U-937, which can be induced to differentiate along the granulocyte/monocyte pathway. Conversely, p93-c-fes expression is absent in the K562 cell line, which is resistant to myeloid differentiation. Upon transfection and clonal selection of K562 cells using a mammalian expression vector containing the 13-kilobase pair c-fes gene, c-fes mRNA was transcribed and p93-c-fes tyrosine activity kinase was expressed. Clones expressing c-fes underwent myeloid differentiation as assessed by the appearance of phagocytic activity, Fc receptors, nitro blue tetrazolium reduction, Mac-1 immunofluorescence, and lysozyme production. These results indicate that the expression of the c-fes protooncogene and its associated tyrosine kinase activity plays a major role in the initiation of myeloid differentiation. 相似文献
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Characterization of a cell-type-restricted negative regulatory activity of the human granulocyte-macrophage colony-stimulating factor gene. 总被引:3,自引:2,他引:1
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J K Fraser J J Guerra C Y Nguyen J E Indes J C Gasson S D Nimer 《Molecular and cellular biology》1994,14(3):2213-2221
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of normal myeloid progenitor cells and can also stimulate the growth of acute myelogenous leukemia (AML) blasts. GM-CSF is not normally produced by resting cells but is expressed by a variety of activated cells including T lymphocytes, macrophages, and certain cytokine-stimulated fibroblasts and endothelial cells. Production of GM-CSF by cultured AML cells has been demonstrated, and GM-CSF expression by normal myeloid progenitors has been postulated to play a role in myelopoiesis. We have investigated the regulation of expression of GM-CSF in AML cell lines, and our results demonstrate the presence of a strong constitutive promoter element contained within 53 bp upstream of the cap site. We have also identified a negative regulatory element located immediately upstream of the positive regulatory element (within 69 bp of the cap site) that is active in AML cell lines but not T cells or K562 CML cells. Competition transfection and mobility shift studies demonstrate that this activity correlates with binding of a 45-kDa protein. 相似文献
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