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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The receptors for interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) consist of two polypeptides each belonging to a new class of molecules referred to as the hemopoietin receptor family. When expressed alone, receptor polypeptides of this family often bind their respective factors with lower affinity than the receptors identified in whole cells. Despite the lack of structural evidence for any enzymatic activity of the receptor polypeptides, both IL-3 and GM-CSF stimulate tyrosine phosphorylation of multiple intracellular substrates. We investigated IL-3 and GM-CSF receptor structure and signaling in a myeloid cell line, FDC-P1, which is dependent on either IL-3 or GM-CSF for growth. Antiphosphotyrosine antibodies were used to immunoprecipitate tyrosine-phosphorylated proteins from 32P-labeled cells or to probe immunoblots. Both IL-3 and GM-CSF stimulated the phosphorylation of a similar pattern of polypeptides on tyrosine. One tyrosine phosphorylated polypeptide migrated with M(r) = 135,000 and increased to 150,000 over a period of 10 min following stimulation of cells with IL-3 or GM-CSF. The M(r) = 135,000-150,000 polypeptide phosphorylated in response to IL-3 was shown to be primarily the Aic-2A polypeptide, the low affinity IL-3 receptor. Phosphatase treatment showed that the dramatic IL-3-induced shift in apparent molecular weight from M(r) = 125,000 in unstimulated cells was entirely due to phosphorylation. The closely related receptor, Aic-2B, was also tyrosine phosphorylated in response to IL-3, although to a lesser extent than Aic-2A. Treatment with GM-CSF resulted in tyrosine phosphorylation of the Aic-2B polypeptide exclusively. It was intriguing that GM-CSF treatment did affect the mobility of the Aic-2A polypeptide on polyacrylamide gels. Together, these results suggest that the Aic-2A polypeptide is part of the IL-3 receptor complex, but not the GM-CSF receptor. In contrast, the Aic-2B polypeptide is a component of the GM-CSF receptor, but it can also be utilized in an IL-3 receptor.
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PMID:Tyrosine phosphorylation of receptor beta subunits and common substrates in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. 140 Apr 95

Two receptor polypeptides have been identified in several studies by using cross-linking with interleukin 3 (IL-3). It has been suggested that proteolytic degradation of the larger polypeptide yields the lower molecular weight fragment, but there is little proof that this is the case. We have used several different approaches to characterize the polypeptides cross-linked in R6X or FDC-P1 cells. Several bifunctional cross-linkers of various sizes were tested to determine their effectiveness in cross-linking IL-3 to its receptor. The longer cross-linker gave the highest proportion of labeling of the low molecular weight band. Incubation in the absence of protease inhibitors caused a decrease in labeling of both cross-linked polypeptides, but no indication of a significant increase in the lower molecular weight band. Direct comparison of the two cross-linked polypeptides by V8 protease mapping showed no common peptides that might be expected if they were related molecules, except those derived from the iodinated IL-3. Digestion with N-glycanase resulted in a decrease in apparent molecular weight of 5000 in the larger polypeptide but a decrease of 15,000 in the smaller polypeptide. These results suggest that the 70-kd polypeptide identified by cross-linking of IL-3 represents a second binding chain of the receptor. By analogy with some of the other hemopoietin receptors, the 70- and 125-kd polypeptides may form a complex necessary for high affinity binding.
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PMID:Two polypeptides identified by interleukin 3 cross-linking represent distinct components of the interleukin 3 receptor. 156 67

Erythrocyte development in mammals depends in part upon the interaction of the glycopeptide hormone erythropoietin (EPO) with cell surface receptors on committed erythroid progenitor cells. Both this factor and an EPO receptor polypeptide previously have been cloned, yet little is presently understood concerning molecular mechanisms of receptor activation and signal transduction. To identify cytosolic receptor domains necessary for signaling, we have compared the activities of a series of deletionally mutated EPO receptor constructs by their expression in interleukin 3-dependent, myeloid FDC-P1 cells. EPO-induced growth was transduced efficiently in these cells by the full-length receptor (507 amino acids), and no measurable loss in activity resulted from the deletion of up to 111 carboxyl-terminal residues. In contrast, the deletion of 44 additional residues led to a dramatic loss (86.3% +/- 7.8%; mean +/- SD) in the ability of this receptor to mediate EPO-induced growth, thus indicating that residues between Gly-352 and Met-396 constitute a functionally critical cytosolic subdomain. Interestingly, the expression of full-length EPO receptors in FDC-P1 cells also led to a selective inhibition of normal proliferative responsiveness to the alternative hematopoietic factor granulocyte-macrophage colony-stimulating factor. Moreover, this inhibition was progressively reversed in forms of the EPO receptor in which distal cytosolic residues were sequentially deleted. These results suggest that EPO receptors normally may trans-modulate components in the pathway of granulocyte-macrophage colony-stimulating factor-induced proliferation and that this down-modulation, as exerted by intact EPO receptors, may play a role in promoting erythroid commitment during myeloid blood cell development.
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PMID:Localized cytosolic domains of the erythropoietin receptor regulate growth signaling and down-modulate responsiveness to granulocyte-macrophage colony-stimulating factor. 171 Dec 11

Interleukin-3 (IL-3) is a lymphokine which stimulates the proliferation of normal and transformed multilineage hematopoietic cells. Recently we reported that bryostatin 1, a macrocyclic lactone and potent activator of protein kinase C, could stimulate normal multipotential hematopoietic progenitor cells in vitro in the absence of added polypeptide growth factors. We have now used the murine IL-3-dependent cell line FDC-P1, derived from normal murine marrow cells, to examine the early biochemical events associated with stimulation of hematopoietic cells. We find that both IL-3 and bryostatin 1 are mitogenic and stimulate the growth of FDC-P1 cells. Cells grown for extended periods in the presence of bryostatin 1 (1 nM) alone retain IL-3 responsiveness, indicating that bryostatin 1 does not induce an IL-3-independent state. Protein phosphorylation studies in cells treated with either IL-3 or bryostatin 1 indicate that both stimulators can mediate the rapid (within 5 min) serine-specific phosphorylation of several nuclear envelope polypeptides, including lamin B. Both IL-3- and bryostatin 1-mediated nuclear envelope phosphorylation is dose-dependent, occurring at concentrations which are mitogenic to FDC-P1 cells. The extent of nuclear envelope phosphorylation mediated by IL-3 and bryostatin 1 correlates with the mitogenic response. Furthermore, both mitogens mediate the rapid immunologic translocation of protein kinase C to the nuclear envelope where phosphorylation occurs. These data indicate that the early mitogenic signal(s) generated by IL-3 and bryostatin 1 may converge at the level of the nuclear envelope, perhaps through a protein kinase C-like activity which mediates phosphorylation of specific nuclear envelope polypeptides such as lamin B.
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PMID:Interleukin-3 and bryostatin 1 mediate rapid nuclear envelope protein phosphorylation in growth factor-dependent FDC-P1 hematopoietic cells. A possible role for nuclear protein kinase C. 260 93

Corncobs, which are distinct morphological units formed by the ordered coaggregation of a filamentous microorganism and streptococci, can be made in vitro by using oral strains of Fusobacterium nucleatum and Streptococcus sanguis. Previous studies have shown that strains of F. nucleatum contain one of at least two different types of corncob receptor. The objective of this study was to isolate the receptor from F. nucleatum ATCC 10953 as the first step in the elucidation of the molecular basis of corncob formation. The cell envelope fraction from this bacterium was treated with trypsin, delipidated with chloroform-methanol, and subjected to ion-exchange chromatography. A single polypeptide (apparent Mr, 39,500), which was eluted from the column with 0.5 M sodium chloride and extracted with dodecyltrimethylammonium bromide to remove contaminating lipopolysaccharide, inhibited corncob formation between strain ATCC 10953 and S. sanguis CC5A. Similarly derived cell fractions from either F. nucleatum FDC 364 or Fusobacterium necrophorum failed to effect coaggregation in the inhibition assay. Amino acid analysis of the polypeptide showed a moderately hydrophobic character (polarity index, 41) and 11% basic residues. Antiserum made against the purified polypeptide agglutinated F. nucleatum ATCC 10953, neutralized the ability of this bacterium to form corncobs, and agglutinated whole cells of S. sanguis CC5A that were precoated with the receptor polypeptide. The identification and isolation of this receptor should greatly enhance our ability to define some of the complex intergeneric coaggregation mechanisms that are thought to occur in the human oral cavity.
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PMID:Isolation of a corncob (coaggregation) receptor polypeptide from Fusobacterium nucleatum. 291 93

In chronic myeloid leukemia (CML), a chromosome translocation has fused the bcr gene to the c-abl oncogene, such that a chimeric bcr-abl polypeptide can be made. To explore the biological properties of bcr-abl and compare them with those of the Abelson virus (AMuLV) transforming gene (gag-v-abl), we have used either a synthetic bcr-v-abl gene that mimics the translocation product or, in some experiments, a bcr-c-abl cDNA. A new retroviral vector was used to introduce the genes into the factor-dependent myeloid line FDC-P1. Both bcr-abl and v-abl efficiently rendered the myeloid cells factor independent and tumorigenic. Their fully autonomous growth may be due to the myeloid growth factor interleukin-3 (IL-3) made in small amounts by the infected cells. Hence autocrine factor production may feature in CML development and Abelson virus transformation.
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PMID:bcr-abl oncogene renders myeloid cell line factor independent: potential autocrine mechanism in chronic myeloid leukemia. 314 34

WEHI-3B myelomonocytic leukaemia cells secrete a haemopoietic cell growth factor (HCGF) which facilitates the proliferation and development of multipotential stem cells and committed progenitor cells. Several cloned, nonleukaemic cell lines (FDC-P cells) are absolutely dependent on HCGF and die in the absence of it. In these cell lines, factor dependence is associated with the ability of HCGF to increase glucose uptake, thereby controlling glycolytic flux and intracellular ATP levels. We have now investigated the effects of HCGF on glucose uptake in WEHI-3B cells. At 20 degrees C 2-deoxyglucose uptake could be stimulated by the addition of HCGF to the extracellular medium. L-glucose uptake was markedly lower than 2-deoxyglucose uptake and did not respond to the addition of HCGF. At 37 degrees C no HCGF stimulation of 2-deoxyglucose uptake was found. However, at this temperature HCGF release from WEHI-3B cells was markedly higher than at 20 degrees C. Our experiments indicate that HCGF stimulates the glucose transport system in both WEHI-3 cells and FDC-P cells. The similarities between the WEHI-3B cell and FDC-P2 cell polypeptide phenotype were investigated using two-dimensional isoelectric focussing/poly-acrylamide gel electrophoresis. This revealed a high degree of correlation between the two cell types in their protein constituents, indicating a close relationship between the normal and leukaemic cells. These similarities between WEHI-3B cells and FDC-P2 cells are considered and their relevance to haemopoiesis and leukaemogenesis is discussed.
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PMID:Stimulation of hexose uptake by haemopoietic cell growth factor occurs in WEHI-3B myelomonocytic leukaemia cells: a possible mechanism for loss of growth control. 388 26

A detailed structure-function analysis of human interleukin 5 (hIL5) has been performed. The hIL5 receptor is composed of two different polypeptide chains, the alpha and beta subunits. The alpha subunit alone is sufficient for ligand binding, but association with the beta subunit leads to a 2- to 3-fold increase in binding affinity. The beta chain is shared with the receptors for IL3 and granulocyte/macrophage-colony-stimulating factor--hence the descriptor beta C (C for common). All hIL5 mutants were analyzed in a solid-phase binding assay for hIL5R alpha interaction and in a proliferation assay using IL5-dependent cell lines for receptor-complex activation. Most residues affecting binding to the receptor alpha subunit were clustered in a loop connecting beta-strand 1 and helix B (mutants H38A, K39A, and H41A), in beta-strand 2 (E89A and R91A; weaker effect for E90A) and close to the C terminus (T109A, E110A, W111S, and I112A). Mutations at one position, E13 (Glu13), caused a reduced activation of the hIL5 receptor complex. In the case of E13Q, only 0.05% bioactivity was detected on a hIL5-responsive subclone of the mouse promyelocytic cell line FDC-P1. Moreover, on hIL5-responsive TF1 cells, the same mutant was completely inactive and proved to have antagonistic properties. Interactions of this mutant with both receptor subunits were nevertheless indistinguishable from those of nonmutated hIL5 by crosslinking and Scatchard plot analysis of transfected COS-1 cells.
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PMID:Identification of receptor-binding domains on human interleukin 5 and design of an interleukin 5-derived receptor antagonist. 776 72

An IgG1 mAb 1G10 derived from an autoimmune MRL/Mp-Ipr/Ipr (MRL/Ipr) mouse has previously been shown to induce IL-3, TNF-alpha and IL-6 production, and autocrine growth in an IL-3-dependent myeloid cell line, FDC-P2/185-4. In the present study, we have attempted to further define the molecular mechanism responsible for the 1G10-induced activation of FDC-P2/185-4 cells. We have shown that 1G10 lacked anti-IgG1 rheumatoid factor activity, failing to generate self-associated immune complexes. Since 1G10 stimulated cells in an Fc gamma R-dependent manner, it seems likely that cross-linking of a cell surface antigen and Fc gamma R by 1G10 antibody is responsible for the stimulation of FDC-P2/185-4 cells. Among several mAb specific to surface antigens expressed on FDC-P2/185-4 cells (MHC class I, LFA-1, and Fc gamma R), only a mAb specific to the alpha chain of LFA-1 alpha was able to induce the IL-3 and Fc gamma R-dependent proliferation of FDC-P2/185-4 cells, similar to that induced by 1G10. Immunoprecipitation analysis revealed that 1G10 recognized a polypeptide with a molecular mass of 140 kilodaltons (p140), which differed from Fc gamma R and from LFA-1 alpha chain. These results suggest that cross-linking of not general but particular cell surface antigens and Fc gamma R stimulates FDC-P2/185-4 cells to produce cytokines resulting in their proliferation.
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PMID:An autoimmune MRL/Mp-Ipr/Ipr mouse-derived monoclonal IgG antibody stimulates cytokine production in bone-marrow-derived cell line by cross-linking of a cell surface antigen and Fc receptor. 802 11

Hepatocyte growth factor (HGF), a mesenchymal-derived polypeptide, stimulates growth, motility and morphogenesis of various types of cells, most predominantly of epithelial cells. We have now identified an additional biological activity of HGF; this factor probably has a role in early hematopoiesis. We examined the effects of HGF on the growth of various murine hematopoietic progenitor tumor cell lines and found that HGF stimulated DNA synthesis in the myeloid leukemia cell line, NFS-60. The mitogenic effect of HGF on NFS-60 cells was additive with the effect of interleukin 3 (IL-3). On the other hand, HGF had no apparent effect on other myeloid leukemia cell lines examined, such as DA-3 and FDC-P1 cells. Scatchard analysis of specific binding of [125I]HGF revealed expression of a high-affinity HGF receptor on NFS-60 and DA-3 cells, but not on FDC-P1 cells. Expression of c-met mRNA correlated well with the existence of a high-affinity HGF receptor. Since the myeloid leukemia cell lines used are cells in the early stage of myeloid differentiation, HGF may play a role in early hematopoiesis.
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PMID:Hepatocyte growth factor stimulates growth of hematopoietic progenitor cells. 839 36


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