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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic labeling of simian virus 40-immortalized murine macrophages with 32Pi and immunoblotting with antibodies to phosphotyrosine demonstrated that the c-fms proto-oncogene product (colony-stimulating factor 1 [CSF-1] receptor) was phosphorylated on tyrosine in vivo and rapidly degraded in response to CSF-1. Stimulation of the CSF-1 receptor also induced immediate phosphorylation of several other cellular proteins on tyrosine. By contrast, the mature cell surface glycoprotein encoded by the v-fms oncogene was phosphorylated on tyrosine in the absence of CSF-1, suggesting that it functions as a ligand-independent kinase.
Mol Cell Biol 1988 Apr
PMID:Ligand-induced tyrosine kinase activity of the colony-stimulating factor 1 receptor in a murine macrophage cell line. 283 54

The bone marrow is a complex microenvironment made up of multiple cell types which appears to play an important role in the maintenance of hematopoietic stem cell self-renewal and proliferation. We used murine long-term marrow cultures and a defective recombinant retrovirus vector containing the simian virus 40 large T antigen to immortalize marrow stromal cells which can support hematopoiesis in vitro for up to 5 weeks. Such cloned cell lines differentially supported stem cells which, when transplanted, allowed survival of lethally irradiated mice, formed hematopoietic spleen colonies in vivo, and stimulated lymphocyte proliferation in vitro. Molecular and functional analyses of these cell lines did not demonstrate the production of any growth factors known to support the proliferation of primitive hematopoietic stem cells. All cell lines examined produced macrophage colony-stimulating factor. The use of immortalizing retrovirus vectors may allow determination of unique cellular proteins important in hematopoietic stem cell proliferation by the systematic comparison of stromal cells derived from a variety of murine tissues.
Mol Cell Biol 1988 Sep
PMID:Generation of murine stromal cell lines supporting hematopoietic stem cell proliferation by use of recombinant retrovirus vectors encoding simian virus 40 large T antigen. 285 29

The normal cellular counterpart of the v-fms oncogene product is a receptor for the mononuclear phagocyte colony-stimulating factor, CSF-1. An interleukin-3 (IL-3)-dependent mouse myeloid cell line, FDC-P1, was infected with a murine retrovirus vector containing v-fms linked to a gene encoding resistance to neomycin (neo). Infected cells selected for resistance to the aminoglycoside G418 contained few proviral DNA copies per haploid genome, expressed low levels of the v-fms-coded glycoprotein, remained IL-3 dependent for growth, and were nontumorigenic in nude mice. In contrast, infected cells selected for their ability to grow in the absence of IL-3 contained an increased number of proviral insertions, expressed high levels of the v-fms-coded glycoprotein, and were tumorigenic in nude mice. The IL-3-independent cells expressed IL-3 receptors of comparable number and affinity to those detected in uninfected FDC-P1 cells and did not produce a growth factor able to support replication of the parental cells. Thus, the synthesis of high levels of the v-fms gene product in FDC-P1 cells abrogated their requirement for IL-3 and rendered the cells tumorigenic by a nonautocrine mechanism. The data suggest that v-fms encodes a promiscuous tyrosine kinase able to transform cells of the myeloid lineage that do not normally express CSF-1 receptors.
Mol Cell Biol 1987 May
PMID:The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1. 303 31

NIH 3T3 cells cotransfected with the human c-fms proto-oncogene together with a 1.6-kilobase cDNA clone encoding a 256-amino-acid precursor of the human mononuclear phagocyte colony-stimulating factor CSF-1 (M-CSF) undergo transformation by an autocrine mechanism. The number of CSF-1 receptors on the surface of transformed cells was regulated by ligand-induced receptor degradation and was inversely proportional to the quantity of CSF-1 produced. A tyrosine-to-phenylalanine mutation at position 969 near the receptor carboxyl terminus potentiated its transforming efficiency in cells cotransfected by the CSF-1 gene but did not affect receptor downmodulation. CSF-1 was synthesized as an integral transmembrane glycoprotein that was rapidly dimerized through disulfide bonds. The homodimer was externalized at the cell surface, where it underwent proteolysis to yield the soluble growth factor. Trypsin treatment of viable cells cleaved the plasma membrane form of CSF-1 to molecules of a size indistinguishable from that of the extracellular growth factor, suggesting that trypsinlike proteases regulate the rate of CSF-1 release from transformed cells. The data raise the possibility that this form of membrane-bound CSF-1 might stimulate receptors on adjacent cells through direct cell-cell interactions.
Mol Cell Biol 1987 Jul
PMID:Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes. 303 46

When 5-fluorouracil (5-FU) resistant bone marrow (BM) cells are depleted of B-cells and then cultured in insert chambers [separated from a layer of adherent BM (aBM) cells by a nucleopore membrane], no mature, lipopolysaccharide (LPS) reactive B-cells are formed. Factors acting on B-cell precursors are not produced unless nonadherent accessory cells have been cultured with aBM cells in the surrounding well. Moreover, soluble products are insufficient to induce differentiation of B-cell precursors unless the cells have been conditioned by direct contact with aBM cells. Such preconditioned precursors complete differentiation when cultured with IL-3 plus IL-1 in dishes coated with fibronectin. In cultures supplemented with IL-3, IL-1 and fibronectin, a pleomorphic layer of aBM cells is generated after a few days. This is not the case in cultures lacking IL-3. Therefore, an important function of IL-3 may be to recruit an adherent accessory cell type from the pool containing precursors of the B-cell as well as myeloid lineages. This view is further supported by experiments on the generation of colonies containing antibody secreting B-cells from day 15 fetal liver precursors which depends on soluble products secreted by aBM cells. When aBM cells established in the absence of IL-3 are present, more than one cell type (or cell product) is limiting. However, if aBM cell layers are generated in the presence of IL-3, only B-cell precursors seem to be limiting. Since macrophages play an important role in the aBM population, the effect of CSF-1 was investigated. Even though CSF-1 potentiates the effect of IL-3 and IL-1, it cannot replace these interleukins. Like IL-3, it may influence B-cell differentiation in an indirect manner by modifying the microenvironment. Another important function of macrophages seems to be related to the production of C3, which binds to CR2 after degradation. P14, a peptide of the CR2 binding C3d fragment, strongly inhibits maturation of B-cell progenitors. A larger CR2 binding peptide, P28, is inhibitory at low concn but stimulatory at higher concn. It is assumed that aggregated P28 may cross-link with CR2 and thereby transfer a differentiation signal to the cell.
Mol Immunol 1988 Nov
PMID:Functional maturation of murine B lymphocyte precursors--III. Soluble factors involved in the regulation of growth and differentiation. 306 30

The biosynthesis of macrophage colony-stimulating factor 1 (CSF-1) was examined in mouse NIH-3T3 fibroblasts transfected with a retroviral vector expressing the 554-amino-acid product of a human 4-kilobase (kb) CSF-1 cDNA. Similar to results previously obtained with a 1.6-kb human cDNA that codes for a 256-amino-acid CSF-1 precursor, the results of the present study showed that NIH-3T3 cells expressing the product of the 4-kb clone produced biologically active human CSF-1 and were transformed by an autocrine mechanism when cotransfected with a vector containing a human c-fms (CSF-1 receptor) cDNA. The 4-kb CSF-1 cDNA product was synthesized as an integral transmembrane glycoprotein that was assembled into disulfide-linked dimers and rapidly underwent proteolytic cleavage to generate a soluble growth factor. Although the smaller CSF-1 precursor specified by the 1.6-kb human cDNA was stably expressed as a membrane-bound glycoprotein at the cell surface and was slowly cleaved to release the extracellular growth factor, the cell-associated product of the 4-kb clone was efficiently processed to the secreted form and was not detected on the plasma membrane. Digestion with glycosidic enzymes indicated that soluble CSF-1 encoded by the 4-kb cDNA contained both asparagine(N)-linked and O-linked carbohydrate chains, whereas the product of the 1.6-kb clone had only N-linked oligosaccharides. Removal of the carbohydrate indicated that the polypeptide chain of the secreted 4-kb cDNA product was longer than that of the corresponding form encoded by the smaller clone. These differences in posttranslational processing may reflect diverse physiological roles for the products of the two CSF-1 precursors in vivo.
Mol Cell Biol 1988 Nov
PMID:Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs. 326 77

A human macrophage colony-stimulating factor encoded by a 4-kilobase cDNA was expressed with bovine papillomavirus vectors in mouse cells. Pulse-chase analyses revealed that the 62-kilodalton (kDa) translation product was glycosylated, cleaved, and efficiently secreted within 1 h of synthesis. The secreted product contained both N-linked and O-linked oligosaccharide chains. Macrophage colony-stimulating factor was present extracellularly as an 80-kDa homodimer and as a multimeric species of greater than 200 kDa that may be associated with other glycoproteins.
Mol Cell Biol 1988 Nov
PMID:Expression and processing of a recombinant human macrophage colony-stimulating factor in mouse cells. 326 78

Regulation of CSF-1 gene expression was investigated in human monocytes. CSF-1 transcripts were at low or undetectable levels in resting monocytes. However, in monocytes treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), CSF-1 mRNA was increased by 3 h and reached maximal levels by 12 h of drug exposure. When nuclear run-on assays were used, CSF-1 gene transcription was also at low or undetectable levels in resting monocytes but was activated after TPA exposure. TPA-treated monocytes exposed to actinomycin D further demonstrated that the half-life of the CSF-1 mRNA is 0.9 h. The results also demonstrated that the protein synthesis inhibitor, cycloheximide (CHX), increases CSF-1 mRNA levels in both resting and TPA-treated monocytes. These effects of CHX occurred in the absence of detectable increases in CSF-1 gene transcription. Moreover, treatment of monocytes with CHX and actinomycin D demonstrated that inhibition of protein synthesis is associated with stabilization of the CSF-1 transcript. Taken together, these findings indicated that CSF-1 gene expression is controlled at both transcriptional and posttranscriptional levels in human monocytes.
Mol Cell Biol 1988 Sep
PMID:Transcriptional and posttranscriptional regulation of CSF-1 gene expression in human monocytes. 326 72

Gene expression for the four different growth-regulatory proteins for cells of the myeloid hematopoietic cell lineages was analyzed in mouse fetal and extraembryonic tissues at various stages of development. The macrophage growth inducer MGI-1M (colony-stimulating factor 1) was the only myeloid hematopoietic growth regulator detected as both mRNA and bioactive protein during fetal development. This regulator was produced predominantly in extraembryonic tissues, and the production of hematopoietic growth regulators in embryogenesis was regulated by transcriptional and posttranscriptional controls.
Mol Cell Biol 1987 Sep
PMID:Control of hematopoietic cell growth regulators during mouse fetal development. 349 68

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


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