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 leukotriene D4 (LTD4) receptor on rat basophilic leukemia (RBL-1) cell membranes was characterized using a radioligand binding assay. [3H]LTD4 binding to RBL-1 membrane receptors was stereoselective, specific, and saturable. The binding affinity and maximum binding density of [3H]LTD4 to RBL-1 membrane receptors were 0.9 +/- 0.2 nM and 800 +/- 125 fmol/mg protein, respectively. Binding of [3H]LTD4 to the receptors was enhanced by divalent cations (Ca2+, Mg2+, and Mn2+) and inhibited by guanine nucleotides and sodium ions, specifically, indicating that a guanine nucleotide-binding protein may regulate the agonist-receptor interaction. LTD4, LTE4 agonist and antagonist analogs competed with the radioligand in binding to the RBL-1 LTD4 receptors. The binding affinities of these analogs correlated with (a) those determined from the guinea pig lung LTD4 receptors and (b) the pharmacological activities in smooth muscle contraction. LTD4 and related agonists also induced time- and concentration-dependent phosphatidylinositol hydrolysis in RBL-1 cells. The LTD4 induction of inositol 1-phosphate was potent, stereoselective, specific, and was blocked by LTD4 receptor antagonists. The rank order potency of agonist-induced inositol 1-phosphate formation in RBL-1 cells was equivalent to the receptor binding affinity determined using either RBL-1 cell or guinea pig lung membranes. These studies have demonstrated the G protein coupled LTD4 receptors on RBL-1 cell membranes. Binding of agonists to the receptor may activate the G protein-regulated phospholipase C to induce hydrolysis of phosphatidylinositol. The hydrolytic products of phosphatidylinositol, possibly inositol trisphosphate and diacylglycerol, may be the intracellular messengers for LTD4 receptors in RBL-1 cells.
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PMID:Identification and characterization of leukotriene D4 receptors and signal transduction processes in rat basophilic leukemia cells. 303 Oct 59

To study Moloney murine leukemia virus (M-MulV) proteins associated with the integration of proviral DNA into the host chromosome, we isolated endonuclease activities from purified virion preparations of the wild type and two of its replication mutants. A major endonuclease activity was identified in virions of M-MuLV; the enzyme catalyzed nicks in double-stranded DNA in the presence of either Mn2+ or Mg2+ and was stimulated by ATP. The endonuclease nicked DNA adjacent to all four nucleotides with some preference for G and C. The same enzyme, and in comparable amounts, was isolated from two virus replication mutants: dl2905, deficient in the processing of Pr65gag and Pr200gag-pol, and dl50401, deficient for the virus integration function. In the process of these experiments, the residual reverse transcriptase in mutant dl2905 was shown to be the mature size, implying that the uncleaved precursor lacks enzymatic activity. It appears that the major endonuclease activity found in virions of M-MuLV is not encoded by either the gag or pol genes.
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PMID:Characterization of endonuclease activities in Moloney murine leukemia virus and its replication-defective mutants. 303 6

Two tyrosine protein kinase activities have been identified previously to be present in HL-60 leukemia cells during induction of granulocytic and monocytic differentiation with a variety of differentiating agents. We have copurified a membrane-associated tyrosine kinase (p93) and an activity associated with both the cytosol and membrane fractions (p60). Triton X-100 extracts from HL-60 cells treated with dimethyl sulfoxide were subjected to tyrosine-agarose chromatography, polypropyl aspartamide high performance liquid chromatography (HPLC), and HPLC using an antiphosphotyrosine IgG-derivatized column. Overall purification was 2700-fold for p93 and 1800-fold for p60. p60 and p93 are phosphorylated exclusively on tyrosine residues and can use poly(Glu,Tyr)4:1, histone H1 and vasoactive intestinal peptide as substrates. Poly(Glu,Tyr)1:1 and poly(Glu,Ala,Tyr)6:3:1 were less effective substrates for p60 and p93. The activity of p93 was dependent on Mg2+ or Mn2+, whereas p60 was dependent on Mg2+; however, the activity of p60 was stimulated in a synergistic manner by the presence of both Mg2+ and Mn2+, whereas the activity of p93 was not enhanced further by the combination of divalent ions. Both p60 and p93 were immunoprecipitated by an anti-v-src monoclonal antibody but only p93 was immunoprecipitated by an anti-v-fps/fes antibody. V8 protease digestion of p60 revealed one major proteolytic fragment containing phosphotyrosine, whereas V8 protease digestion of p93 produced two major peptides that were phosphorylated on tyrosine residues. These results suggest that, although p93 and p60 may possess some epitopic similarities, they have distinguishing phosphorylation sites. Moreover, p93, in contrast to p60, appears to be strictly associated with granulocytic/monocytic differentiation and related to the cellular fps/fes protooncogene.
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PMID:Purification and characterization of p93fes- and p60src-related tyrosine protein kinase activities in differentiated HL-60 leukemia cells. 348 Feb 86

Bis(diphenylphosphine)ethane (DPPE) and its bis[chlorogold(I)] [DPPE(Au2Cl2)], and bis[trichlorogold(III)] [DPPE(Au2Cl6)], complexes have in vivo antitumor activity. To determine if interaction with metals in situ can play a role in the antitumor activity of DPPE, we have studied the effects of DPPE, DPPE(Au2Cl2), DPPE(Au2Cl6) and mixtures of DPPE with metal salts on in vitro and in vivo biological systems. The in vitro cytotoxic potencies of the two DPPE-gold complexes were approximately 10-fold greater than that of DPPE. In addition, the cytotoxic potency of DPPE was increased when incubated with cells in the presence of Au(III) and Cu(II) salts, whereas Mg(II), Zn(II), Mn(II), Fe(II), Co(II), and Cd(II) had no effect. The effects of DPPE, DPPE(Au2Cl2) and mixtures of DPPE and metal salts on the activity of a model enzyme system, DNA polymerase alpha were measured. While DPPE did not inhibit the activity of DNA polymerase alpha, the DPPE(Au2Cl2) complex and mixtures of DPPE and Cu(II) salts inhibited the activity of the enzyme. Consistent with the effects observed in vitro, coadministration of Cu(II) or Au(III) increased the in vivo potency of DPPE in mice bearing i.p. P388 leukemia. Fifteen other DPPE analogues were evaluated for in vivo antitumor activity and for the effect of Cu(II) on their in vitro cytotoxic potency; there was a relationship between the ability of Cu(II) to potentiate the cytotoxic activities of DPPE analogues and their having in vivo antitumor activity.
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PMID:Modulation of the antitumor and biochemical properties of bis(diphenylphosphine)ethane with metals. 375 63

High level of tyrosine protein kinase activity was found in a membrane fraction isolated from an acute myeloblastic leukemia, out of 24 leukemias of different origin investigated. The major substrate for tyrosine phosphorylation in vitro was a 58 kDA protein (p58). The phosphorylation proceeded actively at 0 degrees C and was strongly stimulated by Mn2+ ions. Comparison by partial proteolysis of the p58 with similar phosphoproteins from a T-lymphoma line (KE37) and from lectin stimulated lymphocytes showed high similarity. The possible role of the tyrosine kinase activity in this leukemia is discussed.
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PMID:Acute myeloblastic leukemia with active tyrosine protein kinase. 386 16

The influence of the diterpene, forskolin, was studied on adenylate cyclase activity in membranes of rat basophilic leukemia cells. Forskolin increased basal adenylate cyclase activity maximally 2-fold at 100 microM. However, adenylate cyclase activity stimulated via the stimulatory guanine nucleotide-binding protein, Ns, by fluoride and the stable GTP analog, guanosine 5'-O-(3-thiotriphosphate), was inhibited by forskolin. Half-maximal and maximal inhibition occurred at about 1 and 10 microM forskolin, respectively. The inhibition occurred without an apparent lag phase, whereas the enzyme stimulation by forskolin was preceded by a considerable lag period. The inhibition was not affected by treating intact cells or membranes with pertussis toxin and proteolytic enzymes, respectively, which have been shown in other cell types to prevent adenylate cyclase inhibition mediated by the guanine nucleotide-binding regulatory component, Ni. The forskolin inhibition of the stable GTP analog-activated adenylate cyclase was impaired by increasing the Mg2+ concentration and was reversed into a stimulation by Mn2+. Under optimal inhibitory conditions, forskolin even decreased basal adenylate cyclase activity. Finally, forskolin largely reduced the apparent affinity of the rat basophilic leukemia cell adenylate cyclase for its substrate, MgATP, which reduction resulted in an apparent inhibition at low MgATP concentrations and a loss of the inhibition at higher MgATP concentrations. The data indicate that forskolin can cause both stimulation and inhibition of adenylate cyclase and, furthermore, they suggest that the inhibition may not be mediated by the Ni protein, but may be caused by a direct action of forskolin at the adenylate cyclase catalytic moiety.
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PMID:Stimulation and inhibition of rat basophilic leukemia cell adenylate cyclase by forskolin. 389 83

RNA tumor viruses contain a characteristic RNA-dependent DNA polymerase (reverse transcriptase) which has been thought to be related to the induction of leukemia by this virus. A disturbance in a zinc-dependent enzyme system was first postulated to account for the demonstrated differences in zinc metabolism of normal and leukemic leukocytes [Vallee et al. in (1949) Acta Unio. Int. Contra Cancrum 6, 869 and (1950) Acta Unio. Int. Contra Cancrum 6, 1102]. In order to investigate the relationship between zinc and the initiation of leukemia in chickens by avian myeloblastosis virus, we have examined the metalloenzyme nature of its reverse transcriptase. The present data show that this protein is a zinc metalloenzyme demonstrating the postulated relationship between zinc and a leukemic process. Paucity of purified enzyme generated the design of a novel system of analysis incorporating microwave-induced emission spectrometry combined with gel exclusion chromatography. It provides precision, reproducibility, and remarkable limits of detection on mul samples containing 10(-12) to 10(-14) g-atoms of metal, and is thus orders of magnitude more sensitive than other methods. The chromatographic fraction with highest enzymatic activity contains 1.8 x 10(-11) g-atoms of zinc per 1.6 mug of protein, corresponding to either 1.8 or 2.0 g-atoms of zinc per mole of enzyme for a molecular weight previously determined either as 1.6 or 1.8 x 10(5). Copper, iron and manganese are absent, i.e., at or below the limits of detection, 10(-13) to 10(-14) g-atoms. Agents known to chelate zinc inhibit the enzyme, while their nonchelating isomers do not. The data underline the participation of zinc in nucleic acid metabolism and bear importantly upon the lesions that accompany leukemia and zinc deficiency.
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PMID:RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus: a zinc metalloenzyme. 413 17

The RNA-dependent DNA polymerase(s) in murine leukemia, murine mammary tumor, and avian myeloblastosis viruses require maganese for optimal activity. The transcription of added synthetic polyribonucleotides is greatly enhanced when manganese is used in place of magnesium. A soluble RNA-dependent DNA polymerase activity has been released from murine leukemia particles in the presence of manganese and high detergent concentrations. Two RNA viruses, visna virus of sheep and a primate syncytial virus, not known to have tumor-producing ability, also contain the polymerase.
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PMID:RNA-dependent DNA polymerase activity in five RNA viruses: divalent cation requirements. 432 57

A DNA polymerase activity that promotes the synthesis of poly(dT) has been found in association with intracisternal A-type particles isolated from several mouse tumors. The poly(dT) synthesis activity requires a DNA or RNA primer, is optimal at high salt concentration, prefers magnesium over manganese, and is stimulated by poly(rA). No significant incorporation of dAMP, dGMP, or dCMP was detected in the presence of several RNA and DNA template-primers. The enzyme activity differs in several of its properties from the poly(rA)-directed DNA polymerase activity associated with Rauscher murine leukemia virus.
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PMID:A novel DNA polymerase activity found in association with intracisternal A-type particles. 450 67

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


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