Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The met oncogene was previously isolated from a chemically transformed human cell line, MNNG-HOS. Recent evidence has demonstrated that two classes of transcripts are expressed from the met proto-oncogene locus. The met oncogene, however, expresses an aberrant RNA which has sequences in common with both transcripts. We now report partial nucleotide sequencing of the human met oncogene and show that met is related to the protein kinase oncogenes and growth factor receptors. The met nucleotide sequence is not identical to that of any published gene, and it is more closely homologous to the tyrosine kinases than to the serine/threonine kinases. Within the tyrosine kinase family, the sequenced met domains are most closely related to the human insulin receptor and the viral abl gene. In situ chromosome hybridization has mapped met to human chromosome 7 band 7q21-q31, a location distinct from that of other kinases. This is also a region associated with nonrandom chromosomal deletions observed in a portion of patients with acute nonlymphocytic leukaemia. The accompanying paper shows that this chromosomal locus is also tightly linked with the human heredity disease cystic fibrosis.
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PMID:The human met oncogene is related to the tyrosine kinase oncogenes. 406 11

Human T-cell leukemia virus producer cell line MT-2 was labeled with [32P]phosphoric acid, and its cell extracts were immunoprecipitated with mouse monoclonal antibodies (GIN-7, and KK-1) and rabbit sera (anti-p24, and anti-gp68). Analysis of the immunocomplexes on sodium dodecyl sulfate-polyacrylamide gell electrophoresis revealed that p53, p28, and p19 of adult T-cell leukemia-associated antigens were phosphorylated in vivo. Immunocomplexes of MT-2 cell extract with monoclonal antibody KK-1 were incubated with [gamma-32P]ATP in vitro and it was revealed that the phosphokinase activity was associated with p28. The phosphokinase activity of p28 was specific to the serine residue but was not to the tyrosine residue.
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PMID:28,000-dalton polypeptide (p28) of adult T-cell leukemia-associated antigen encoded by 24 S mRNA of human T-cell leukemia virus has an associated protein kinase activity. 608 30

Immunofluorescent staining of HeLa cells with rabbit antiserum raised against isolated HeLa cell nucleoli showed bright nucleolar fluorescence. Immunoprecipitation of nuclear extracts obtained from HeLa cells labelled with 35S-methionine or 32P-orthophosphate followed by gel electrophoresis of the precipitate revealed a major band of 90 kd. This antigen, called pp90, was judged to be responsible for the nucleolar fluorescence. Serine residues were predominantly phosphorylated in pp90. Similar nucleolar fluorescence was observed commonly in human cells derived from malignant tumors including acute lymphatic leukemia, adult T-cell leukemia, hepatitis B virus-associated hepatoma, adenocarcinoma, and in 5 lymphoid cells derived from Burkitt lymphoma but not in normal human lymphocytes or liver cells. In immunoprecipitation, 32P-labelled pp90 was commonly detected as the major component in all of those cells which showed nucleolar fluorescence. Resting human embryo lung (HEL) cells were negative for both nucleolar fluorescence and pp90 in immunoprecipitation, but turned positive when stimulated to grow, suggesting the involvement of pp90 in cell growth. Antigen pp90 was also induced in human lymphocytes and HEL cells by infection with Epstein-Barr virus in human cytomegalovirus, respectively, which are known to induce cell DNA synthesis in early stages of infection. A cross-reacting nucleolar antigen was detected in 2 monkey cells but not in 3 rodent cells tested.
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PMID:A human nucleolar antigen (pp90) associated with cell growth and its induction by Epstein-Barr virus and human cytomegalovirus. 609 64

People exposed to type I human T-cell leukemia virus (HTLV-I) develop antibodies to an antigen at the surface of virus-infected cells, designated human T-cell leukemia virus membrane antigen (HTLV-MA). In an earlier study, we demonstrated that the major component of HTLV-MA is gp61, a glycoprotein encoded by the HTLV env gene. In the current study, we found that human antibodies that react with HTLV-MA on cells infected with HTLV-I react equally well with HTLV-MA on C3-44/MO, a target cell infected with type II HTLV. A glycoprotein with an approximate size of 67 kDa, gp67, was identified in C3-44/MO using immunoprecipitation and NaDodSO4/PAGE analysis. The positions of serine and cysteine residues were determined in the amino terminus of gp67 by radiolabel sequencing analysis. Comparison with the amino acid sequence deduced from the primary nucleotide sequence of HTLV-IIMO virus reveals that gp67 is also encoded, at least in part, by the env gene. The gp67 of HTLV-IIMO, like the env gene product of HTLV-ICR, gp61, is recognized both by antibodies from a HTLV-IIMO-infected patient with a variant form of hairy cell leukemia, and by antibodies from patients with HTLV-I-associated adult T-cell leukemia/lymphoma. These results indicate that, despite the divergence between HTLV-I and HTLV-II, the major env gene products of the two types of HTLV are conserved to the degree that they are serologically cross-reactive.
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PMID:Serological cross-reactivity between envelope gene products of type I and type II human T-cell leukemia virus. 609 7

Gallo and his coworkers isolated a retrovirus (HTLV) from human cells derived from T-cell leukemia and lymphoma. Hinuma and his coworkers isolated independently a similar virus from a cell line derived from adult T-cell leukemia (ATL) patient. The occurrence of ATL correlates with the formation of antibody to ATL associated antigens or ATLA. To understand the etiological relationship between ATL and HTLV, we analyzed the antigens termed ATLA and found that they are polypeptides encoded by HTLV genome. We further studied the genome of HTLV and its gene expression in cells as well as in a cell-free translation system. We focused on a defective type HTLV produced from a cell line MT-2 that transforms normal lymphocytes most efficiently. The 24S defective gene of HTLV consists of a fused gene of gag-pXs and is amplified at the proviral state. The in vitro translation experiments revealed that the 24S defective gene of HTLV directs the synthesis of p28 of ATLA. By the sequence analysis of the amplified gag-pXs fused genes, we found that a carboxy terminal portion of p28 is translated from a pX-0 region. We further investigated a function of the gag-pX-0 fusion protein, p28. The p28 has an associated protein kinase activity that requires manganese instead of magnesium and phosphorylates the serine residue specifically. Another defective HTLV with a genomic 32S RNA was analyzed. The 32S defective genomic RNA forms a subgenomic 20S RNA in cells. The 20S mRNA is a transcript of an env-pXs fused genome and directs the synthesis of a fused glycoprotein, gp68 of ATLA. The sequence analysis of a cloned cDNA derived from the subgenomic 20S mRNA revealed that a coding frame of the entire pX-IV region is translated. In fact, an antibody against synthetic polypeptides of the pX-IV, immunoprecipitated the gp68. These results demonstrate at the first time that the pX-0 and pX-IV of HTLV genome are expressed in human cells. The biological activities of the fused pXs proteins are also discussed. Human T-cell leukemia virus type I (HTLV-I), a family of human retrovirus and the predicted causative agent of human adult T-cell leukemia/lymphoma (ATL) consists of the gag, pol, env, and pX regions (1).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pX region of HTLV-I. 610 Jun 40

Leukotriene C4 and leukotriene D4 are slow reacting substances produced by mouse mastocytoma cells and rat basophilic leukemia cells, respectively. Serine x borate complex, an inhibitor of glutamyl transpeptidase (EC 2.3.2.2), prevented the formation of the biologically more potent leukotriene D4 and caused accumulation of leukotriene C4 in rat basophilic leukemia cell suspensions. 5,8,11-Eicosatriynoic acid, a lipoxygenase inhibitor, prevented the biosynthesis of leukotriene C4 (ID50, 5 microM) by mastocytoma cells. The results demonstrate that gamma-glutamyl transpeptidase is involved in the biosynthesis of leukotriene D4 and suggest that leukotriene C4 is formed as an intermediate.
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PMID:Inhibition of leukotriene C and leukotriene D biosynthesis. 610 18

The homogenate of rat basophilic leukemia cells produces both the dihydroxy-leukotrienes and the peptido-leukotrienes (LT) C4, D4 and E4. The enzymes responsible for the formation of LTA4 and LTB4 are in the soluble fraction while the enzymes for LTC4, LTD4 and LTE4 are particulate (10,000 X g pellet). Centrifugation of the 10,000 X g pellet over a sucrose gradient resulted in two subfractions, a membrane fraction and a pellet (sucrose pellet). The fractions were incubated with LTC4, and the products were identified by bioassay, HPLC and UV spectra. The membrane fraction contained the enzymes gamma-glutamyl transpeptidase and amino peptidase which convert LTC4 to LTD4 and LTD4 to LTE4, respectively. When incubated with LTC4, the membrane fraction showed a dose dependent formation of LTD4 and a time course which reached a plateau at 30 to 45 minutes. Addition of serine.borate blocked the formation of LTD4, and cysteine blocked LTE4 production. The sucrose pellet showed little conversion of LTC4 to LTD4. We conclude that the gamma-glutamyl transpeptidase and the amino peptidase which produce LTD4 and LTE4 respectively are plasma membrane bound.
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PMID:Leukotriene D4 and E4 formation by plasma membrane bound enzymes. 615 16

Variants of the rat basophilic leukemia (RBL) cell line were isolated and screened for phospholipid methyltransferase I and II activities, enzymes that convert phosphatidylethanolamine to phosphatidylcholine. Two variants were found that had decreased phospholipid methyltransferase enzyme levels and were unable to cause an influx of Ca2+ or release histamine in an IgE-mediated reaction. However, these cells were able to release histamine through an ionophore-induced reaction, indicating that the releasing mechanism distal to the Ca2+ channel was intact. One cell line, 1C1.B1, had low specific activity for phospholipid methyltransferase I. A second variant, 2H3.B6, had reduced phospholipid methyltransferase II activity. Although both variants were unable to incorporate label from [methyl-3H]methionine or [3H]serine into phosphatidylcholine, they were able to incorporate [methyl-3H]choline and myo-[2-3H(N)]inositol into phospholipids. Fusion of the two cell lines and isolation on selective media resulted in the growth of eight independent hybrids. All eight had an increased number of chromosomes and normal phospholipid methyltransferase activities. Stimulation of the hybrids with IgE resulted in CA2+ influx and histamine release. These results indicate that phospholipid methylation precedes and is necessary for Ca2+ influx, and they further support the hypothesis that methylation is a necessary early step in the IgE-mediated histamine release reaction in RBL cells.
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PMID:Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx, and histamine release: reconstitution by hybridization. 617 12

Specific immune precipitation of immunoglobulin E(IgE)-receptor complexes from detergent extracts of 32P-labeled rat basophilic leukemia cells yielded a phosphoprotein of Mr approximately 35,000 on gel electrophoresis in sodium dodecyl sulfate. This phosphoprotein was shown by several criteria to be the beta chain of the receptor for IgE. Phosphorylation occurs at a serine residue (or residues) in a region (beta 2) of the beta chain that is thought to be exposed on the cytoplasmic face of the plasma membrane. Our results suggest that phosphorylation probably takes place after the insertion of the beta chain into the membrane. The IgE-binding alpha chain of the receptor and the IgE associated with it are not phosphorylated. We have so far been unable to detect any changes in the state of phosphorylation of either chain of the receptor or of IgE itself after IgE-mediated triggering of the cells.
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PMID:Phosphorylation of the receptor of immunoglobulin E. 621 79

Transformation of chicken cells by Fujinami sarcoma virus (FSV), PRC II or Y73 (three independently isolated avian sarcoma viruses that are replication-defective and lack the Rous sarcoma virus src gene) resulted in significant elevation (4-13 fold) of phosphotyrosine levels in cellular protein. The gag-related proteins encoded by these avian sarcoma viruses (ASVs) were all associated with tyrosine-specific protein kinase activity when assayed in immune complexes and were phosphorylated at both tyrosine and serine residues in vivo. Both the phosphotyrosine level in protein of FSV-infected cells and the protein kinase activity assayed in immune complexes containing the FSV protein P140 were temperature-sensitive. The presumed transforming proteins of these ASVs were compared with those of Rous sarcoma virus (RSV), Abelson murine leukemia virus and the Snyder-Theilen and Gardner-Arnstein strains of feline sarcoma virus (FeSV), which have previously been associated with tyrosine-specific protein kinase activity. FSV and PRC II proteins were shown to be structurally related to one another and to the FeSV proteins by tryptic peptide mapping and by immunological studies. No homology was observed, however, between the transforming proteins of RSV, Y73, Abelson murine leukemia virus and the FSV/PRC II/FeSV class, suggesting there may be at least four classes of retroviruses whose transformation mechanisms involve aberrant phosphorylation of cellular protein at tyrosine residues.
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PMID:Transforming proteins of some feline and avian sarcoma viruses are related structurally and functionally. 626 83


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