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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An AU-rich sequence present within the 3' untranslated region has been shown to mark some short-lived mRNAs for rapid degradation. We demonstrate by label transfer and gel shift experiments that a 32-kDa polypeptide, present in nuclear extracts, specifically interacts with the AU-rich domains present within the 3' untranslated region of human granulocyte-macrophage colony-stimulating factor, c-fos, and c-myc mRNAs and a similar domain downstream of the poly(A) addition site of the adenovirus IVa2 mRNA. Competition experiments and partial protease analysis indicated that the same polypeptide interacts with all four RNAs. A single AUUUA sequence in a U-rich context was sufficient to signal binding of the 32-kDa polypeptide. Insertion of three copies of this minimal recognition site led to markedly reduced accumulation of beta-globin RNA, while the same insert carrying a series of U-to-G changes had little effect on RNA levels. Steady-state levels of beta-globin-specific nuclear RNA, including incompletely processed RNA, and cytoplasmic mRNA were reduced. Cytoplasmic mRNA containing the AU-rich recognition sites for the 32-kDa polypeptide exhibited a half-life shorter than that of mRNA with a mutated insert. We suggest that binding of the 32-kDa polypeptide may be involved in the regulation of mRNA half-life.
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PMID:A 32-kilodalton protein binds to AU-rich domains in the 3' untranslated regions of rapidly degraded mRNAs. 190 42

Activation of T cells by antigen, lectin, or a combination of phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) leads to the induction of genes for a set of lymphokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF). We demonstrated in earlier studies that the upstream region of the mouse GM-CSF promoter at positions between -95 and -73 is essential for transcriptional activation in response to PMA/A23187. This region contains two DNA-binding motifs, GM2 and GC-box. The GM2 sequence (GGTAGTTCCC) is recognized by an inducible factor NF-GM2; the other (CCGCCC) by constitutive factors A1, A2, and B. To elucidate the mechanism of GM-CSF gene activation, we have purified the inducible factor NF-GM2 from the nuclear extract of stimulated Jurkat cells on the basis of specific DNA-binding activity. The purified NF-GM2 consists of 50 (p50) and 65 kDa (p65) polypeptides and has a binding activity specific for both the GM-CSF and immunoglobulin kappa (GGAAAGTCCC) enhancers. Electrophoretically purified p50 alone can form a protein-DNA complex, but in the mixture, p50 associates preferentially with p65 to form the NF-GM2 complex. In addition, p65 gave per se, with low affinity, a protein-DNA complex that migrated more slowly than native NF-GM2 complex. Furthermore, an antiserum against KBF1 (identical to 50 kDa NF-kappa B protein) reacted with the p50 of NF-GM2, indicating that the NF-GM2 polypeptide cannot be immunologically differentiated from the 50 kDa subunit of NF-kappa B. The purified NF-GM2 activated in vitro transcription from the kappa B enhancer, while it failed to stimulate transcription from the GM-CSF promoter harboring the GM2 sequence. This suggests that the activation mechanism of the GM-CSF gene through the GM2/GC-box sequence is different from that of genes carrying the kappa B enhancer alone.
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PMID:A nuclear factor NF-GM2 that interacts with a regulatory region of the GM-CSF gene essential for its induction in responses to T-cell activation: purification from human T-cell leukemia line Jurkat cells and similarity to NF-kappa B. 191 48

Human granulocyte colony-stimulating factor (hG-CSF) cDNA was cloned, by using a synthetic oligonucleotide probe, from an Okayama-Berg cDNA library of lipopolysaccharide-stimulated human peripheral blood macrophages. The cDNA encodes a polypeptide with an amino acid sequence which completely matches that of the known polypeptide with hG-CSF activity derived from human tumor cell lines. Expression in E. coli of high levels of the protein (about 10% of total cellular proteins) was accomplished under control of the trp promoter, and the purified protein was proved to have hG-CSF activity. Our data provide evidence that human peripheral blood macrophages do produce hG-CSF mRNA when stimulated exogenously, suggesting they are the producer of naturally occurring hG-CSF.
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PMID:Cloning of granulocyte colony-stimulating factor cDNA from human macrophages and its expression in Escherichia coli. 244 47

1. Colony-stimulating factor (CSF-1) was isolated from a large volume of fresh normal human urine by 5 steps of purification and enrichment. 2. The purification factor is 100,000 fold and the purified compound exhibits a 2.16 x 10(7) U/mg of protein sp. act. 3. The isolated CSF-1 is a sialoglycoprotein with 41.5% of carbohydrate. The almost complete removal of this carbohydrate moiety (up to 91%) was achieved by incubation with trifluoromethane sulfonic acid. 4. The deglycosylated CSF-1 (DG-CSF-1) possesses an apparent Mr 38,000 compared to native CSF-1 with an initial Mr 57,000 (Goa et al., 1988). 5. The features of the interaction of radio-iodinated [125I]CSF-1 with single cell suspensions from various human tissues (bone marrow, spleen, blood, peritoneal cavity, alveolar lavage, lymph node and thymus), were studied. 6. The binding activity of peritoneal macrophages was the highest among the cells examined and erythrocytes, thymus and blood granulocytes showed no CSF-1 binding. 7. On incubation with [125I]CSF-1 at 0 degrees C, cellular binding of [125I]CSF-1 reached a stable maximum within 16 hr. This is in contrast to the association behaviour at higher temperature. 8. At 37 degrees C, cellular associated [125I]CSF-1 levels reached, within 90 min, an unstable maximum which was up to 10 times less than that occurring under the same conditions at 0 degree C. From the Scatchard plot analysis, we obtained the affinity constant and the number of receptor(s). 9. The binding site is sensitive to trypsin. 10. The receptor alone, (labelled by cross-linking to [125I]CSF-1 with di-succinylimidyl-suberate), is a polypeptide with an approx. Mr 110,000. 11. Our results showed that the receptor of CSF-1 is a tyrosin-kinase.
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PMID:The specific binding activities of human urinary radioiodinated colony-stimulating factor-1 to various human tissue cells. 252 35

Two cDNA clones encoding a receptor for human granulocyte-macrophage colony-stimulating factor (hGM-CSF-R) were isolated by expression screening of a library made from human placental mRNA. Pools of recombinant plasmid DNA were electroporated into COS cells which were then screened for their capacity to bind radioiodinated hGM-CSF using a sensitive microscopic autoradiographic approach. The cloned GM-CSF-R precursor is a 400 amino acid polypeptide (Mr 45,000) with a single transmembrane domain, a glycosylated extracellular domain and a short (54 amino acids) intracytoplasmic tail. It does not contain a tyrosine kinase domain nor show homology with members of the immunoglobulin super gene family, but does show some significant sequence homologies with receptors for several other haemopoietic growth factors, including those for interleukin-6, erythropoietin and interleukin-2 (beta-chain) and also to the prolactin receptor. When transfected into COS cells the cloned cDNA directed the expression of a GM-CSF-R showing a single class of affinity (KD = 2(-8) nM) and specificity for human GM-CSF but not interleukin-3. Messenger RNA coding for this receptor was detected in a variety of haemopoietic cells known to display hGM-CSF binding, and cross-linking experiments revealed a similar size for the glycosylated receptors in transfected COS and haemopoietic cells.
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PMID:Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. 255 71

The hemopoietic growth factor granulocyte-macrophage colony-stimulating factor, GM-CSF, specifically controls the production of granulocytes and macrophages. This report describes the binding of biologically-active 125I-labeled murine GM-CSF to a range of hemopoietic cells. Specific binding was restricted to murine cells and neither rat nor human bone marrow cells appeared to have surface receptors for 125I-labeled GM-CSF. 125I-Labeled GM-CSF only appeared to bind specifically to cells in the myelomonocytic lineage. The binding of 125I-labeled GM-CSF to both bone marrow cells and WEHI-3B(D+) was rapid (50% maximum binding was attained within 5 min at both 20 degrees C and 37 degrees C). Unlabeled GM-CSF was the only polypeptide hormone which completely inhibited the binding of 125I-labeled GM-CSF to bone marrow cells, however, multi-CSF (also called IL-3) and G-CSF partially reduced the binding of 125I-labeled GM-CSF to bone marrow cells. Interestingly, the binding of 125I-labeled GM-CSF to a myelomonocytic cell line, WEHI-3B(D+), was inhibited by unlabeled GM-CSF but not by multi-CSF or G-CSF. Scatchard analysis of the binding of 125I-labeled GM-CSF to WEHI-3B(D+) cells, bone marrow cells and peritoneal neutrophils indicated that there were two classes of binding sites: one of high affinity (Kd1 = 20 pM) and one of low affinity (Kd2 = 0.8-1.2 nM). Multi-CSF only inhibited the binding of 125I-labeled GM-CSF to the high affinity receptor on bone marrow cells: this inhibition appeared to be a result of down regulation or modification of the GM-CSF receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells. 299 Sep 15

Colony-stimulating factor 1 (CSF-1) is a glycoprotein growth factor that specifically regulates the survival, proliferation and differentiation of mononuclear phagocytes and their precursors via a cell surface receptor selectively expressed on these cell types. The purified receptor is a single glycosylated polypeptide, Mr 165 000, which exhibits CSF-1-dependent autophosphorylation in tyrosine. CSF-1 alone regulates cells of the mononuclear phagocytic series (CSF-1-dependent colony-forming unit [CFU-C]----monoblast----promonocyte----monocyte----macrophage). However, the presence of a multipotent haemopoietic cell growth factor, haemopoietin-1, permits CSF-1 to stimulate precursors of CFU-C to proliferate and differentiate to macrophages. Precursors of CFU-C possess low levels of the CSF-1 receptor but there is an increase in receptor levels on CFU-C just before their differentiation to adherent, proliferating mononuclear phagocytes. As the timing of this developmentally associated increase in receptor expression coincides with the acquisition of responsiveness to CSF-1 alone, it is an early indicator of determination to the mononuclear phagocytic lineage.
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PMID:Action of the colony-stimulating factor, CSF-1. 301 14

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. The CSF-1 receptor was purified from cell membranes of the J774.2 mouse macrophage cell line by solubilization with Triton X-100, CSF-1 affinity chromatography, and gel filtration. The purified receptor is a protein or glycoprotein of 165 kDa comprising a single polypeptide chain that is not covalently associated, either as a homopolymer, or with any other protein. CSF-1 stimulated autophosphorylation of the purified receptor in tyrosine residues. Casein but not histone was shown to act as a substrate for the tyrosine protein kinase activity of purified receptor.
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PMID:Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity. 302 75

Eosinophil differentiation factor (EDF) is a recently described regulator affecting eosinophil growth and activation. cDNA clones for murine EDF were isolated by direct expression from libraries prepared from the T cell hybrid NIMP-TH1. The longest cDNA clone obtained was 1534 bp in length encoding a polypeptide of 133 amino acids. Two variant cDNAs suggesting alternative RNA processing events were detected. The EDF gene was cloned from a genomic lambda library and a region of 6727 bp encompassing the gene was sequenced. The gene contains three introns 829, 1875 and 79 bases in length and has numerous repetitive sequences. A common, possible regulatory element, including a conserved decamer, lies adjacent to the TATA boxes of the EDF and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes and similar sequences are present in some other lymphokine genes. Recombinant EDF produced in monkey COS cells strongly stimulated the eosinophil lineage and also showed B-cell-growth factor II (BCGFII) activity whereas recombinant murine interleukin-3 and GM-CSF showed much broader activity towards the different myeloid lineages, were less active on eosinophils and had no BCGFII activity. The BCGFII activity of recombinant EDF together with a comparison of the BCGFII (interleukin-5) cDNA sequence with that of the EDF cDNA establishes that these two activities are the properties of a single polypeptide.
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PMID:Isolation, structure and expression of cDNA and genomic clones for murine eosinophil differentiation factor. Comparison with other eosinophilopoietic lymphokines and identity with interleukin-5. 313 8

A cDNA sequence coding for a human granulocyte-macrophage colony-stimulating factor has been isolated from cDNA libraries prepared from mRNA derived from concanavalin A-activated human T-cell clones. The libraries constructed in the pcD vector system were screened by transfecting COS-7 monkey cells with DNA pools to express the products encoded by full-length cDNA inserts. By assaying the cell supernatants, we identified clones encoding a factor that stimulates the formation of granulocyte and macrophage colonies from human progenitor cells. These results demonstrate that identification of full-length cDNAs for many colony-stimulating factors may be achieved entirely on the basis of detecting the functional polypeptide produced in mammalian cells.
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PMID:Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells. 392 54


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