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 pP60gag polyprotein of the feline leukemia virus pseudotype of m1 Moloney murine sarcoma virus [m1MSV(FeLV)] was previously shown to be MSV specific and to contain murine p30 and smaller structural polypeptides. This protein was detected in m1MSV-transformed cells, and in pulse-chase studies it was found to be stable. In this study virion P60 was shown to contain murine pp12, to be phosphorylated, and to bind to nucleic acids. 32P-labeled m1MSV[FeLV) was fractionated by guanidine agarose chromatography and analyzed by gel electrophoresis. Both P60 and pp12 were found to be the major phosphoproteins, phosphorylated in both serine and threonine residues. Virion P60 bound preferentially to single-stranded DNA and RNA in a competition filter binding assay, using 125I-labeled single-stranded calf thymus DNA and various unlabeled nucleic acids. Similar phosphorylation and DNA binding properties were demonstrated for cellular P60. Thus, immunoprecipitation of cellular extracts showed that P60 was phosphorylated in both producer and nonproducer transformed cells, indicating that phosphorylation occurs independently of virus assembly. Moreover, P60 from cytoplasmic extracts was retained on single-stranded DNA-Sepharose columns, demonstrating that cellular P60 binds to DNA.
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PMID:Phosphorylation and nucleic acid binding properties of m1 Moloney murine sarcoma virus-specific pP60gag. 6 21

Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.
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PMID:Urinary amino acid excretion in acute leukemia. 94 16

Signalling proteins such as phospholipase C-gamma (PLC-gamma) or GTPase-activating protein (GAP) of ras contain conserved regions of approximately 100 amino acids termed src homology 2 (SH2) domains. SH2 domains were shown to be responsible for mediating association between signalling proteins and tyrosine-phosphorylated proteins, including growth factor receptors. Nck is an ubiquitously expressed protein consisting exclusively of one SH2 and three SH3 domains. Here we show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues. Similar stimulation of Nck phosphorylation was detected upon activation of rat basophilic leukemia RBL-2H3 cells by cross-linking of the high-affinity immunoglobulin E receptors (Fc epsilon RI). Ligand-activated, tyrosine-autophosphorylated platelet-derived growth factor or epidermal growth factor receptors were coimmunoprecipitated with anti-Nck antibodies, and the association with either receptor molecule was mediated by the SH2 domain of Nck. Addition of phorbol ester was also able to stimulate Nck phosphorylation on serine residues. However, growth factor-induced serine/threonine phosphorylation of Nck was not mediated by protein kinase C. Interestingly, approximately fivefold overexpression of Nck in NIH 3T3 cells resulted in formation of oncogenic foci. These results show that Nck is an oncogenic protein and a common target for the action of different surface receptors. Nck probably functions as an adaptor protein which links surface receptors with tyrosine kinase activity to downstream signalling pathways involved in the control of cell proliferation.
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PMID:The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors. 133 47

Biliary-glycoprotein (BGP), a cell adhesion molecule related to carcinoembryonic antigen (CEA), has been shown to exist as several alternatively spliced isoforms. Here we show that BGPa and BGPb are phosphorylated in the chronic myelogenous leukaemia cell line KG-1, which constitutively expresses several BGP isoforms, and Chinese hamster LR-73 cells transfected with the cDNAs encoding BGPa and BGPb. The phosphorylation can be augmented with the protein tyrosine phosphatase inhibitor ammonium vanadate and with TPA (an activator of protein kinase C). Phospho-amino acid analysis of phosphorylated BGPs demonstrated that phosphorylation occurs on serine, threonine and tyrosine residues. Phosphorylation reactions carried out in in vitro membrane preparations from KG-1 cells revealed a close association of BGP proteins with membrane associated protein tyrosine kinases. These observations suggest an association of BGP proteins with signal transduction molecules which is regulated by alternative splicing of the cytoplasmic domain.
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PMID:Tyrosine phosphorylation of biliary glycoprotein, a cell adhesion molecule related to carcinoembryonic antigen. 137 37

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of the incorporation of [32P]orthophosphate into Rex protein. N-terminal truncation of Rex protein abolished TPA-dependent phosphorylation. Chymotryptic digestion of phosphorylated Rex yielded two phosphopeptides. In vivo phosphorylation sites were identified as serine residues 70 and 177 and threonine residue 174. Serine 70 was a TPA-dependent phosphorylation site within a regulatory domain. We have already shown that the protein kinase C inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) specifically blocked accumulation of viral unspliced gag-pol mRNA. Therefore, the phosphorylation at serine 70 may be involved in the regulation of Rex function in response to extracellular stimuli.
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PMID:Phosphorylation of the Rex protein of human T-cell leukemia virus type I. 140 May 9

Pharmacologic differentiation of the promyelocytic leukemia HL60 is associated with an increase in cellular tyrosine phosphatase activity. We asked (a) if this increase might, at least in part, be due to changes in a transmembranous protein-tyrosine phosphatase, CD45; and (b) if CD45 changes similarly in other differentiating leukemias. Differentiation of HL60, several chronic myelogenous leukemias, a monocytic leukemia (THP-1), and a monoblastoid leukemia (U-937) could be induced by phorbol ester, 1,25-dihydroxy vitamin D3, dimethyl sulfoxide, or cyclic AMP analogues. This differentiation was associated with a marked increase in (a) total cellular tyrosine phosphatase activity (2-4-fold as measured by the ability to dephosphorylate a tyrosine-phosphorylated peptide); (b) CD45-specific tyrosine phosphatase activity (2-4-fold); (c) CD45 cell surface expression by flow cytometry (2-5-fold); (d) synthesis of both exon B-dependent M(r) 205,000 and exon ABC- M(r) 185,000 CD45 proteins, as revealed by immunoprecipitation with antisera specific for CD45 isoforms. Both isoforms have enhanced electrophoretic mobility when isolated from the differentiated cells. This enhanced mobility did not appear to be due to decreased stoichiometry of CD45 phosphorylation on serine/threonine residues. Interestingly, 12-O-tetradecanoylphorbol-13-acetate transiently reduced CD45 protein-tyrosine phosphatase activity in the chronic myelogenous leukemia cell RWLeu4 without altering the CD45 amount (as measured by cell surface immunofluorescence). Modulation of CD45 tyrosine phosphatase activity (and protein levels) may play a role in differentiation or in maintaining cells in a nonproliferative state or may represent a phenotypic marker of differentiation.
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PMID:Differentiation-induced changes in protein-tyrosine phosphatase activity and commensurate expression of CD45 in human leukemia cell lines. 153 52

We report the independent cloning of the cDNA for CD31, a recently described cell adhesion molecule of the immunoglobulin gene superfamily present on platelets, granulocytes, monocytes, lymphocytes, and endothelial cells. Northern analysis revealed three major mRNA transcripts in Jurkat (a human T cell line) and K562 and HEL (leukemia cell lines) cells with an additional 5.3-kilobase transcript seen in cultured human umbilical vein endothelial cells. Following T cell activation, CD31 mRNA was down-regulated by Northern analysis, and decreased CD31 protein expression was confirmed by immunoblots. The down-regulation of CD31 was partially mediated by decreased transcription as demonstrated by nuclear run-on studies. CD31 became rapidly phosphorylated in platelets, Jurkat cells, and endothelial cells after cell activation. We were unable to demonstrate the presence of a phosphotyrosine in CD31 using monoclonal and polyclonal phosphotyrosine antibodies. In addition, CD31 phosphorylation in platelets was induced by phorbol ester and was blocked by staurosporin, a protein kinase C inhibitor, suggesting that CD31 phosphorylation is mediated by protein kinase C and involves serine and/or threonine residues. The phosphorylation of CD31 following cell activation may modulate its cellular adhesiveness, and the down-regulation of its expression may serve to impart target specificity and to localize effector lymphocytes to areas of inflammation.
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PMID:The cell adhesion molecule CD31 is phosphorylated after cell activation. Down-regulation of CD31 in activated T lymphocytes. 154 7

Human granulocyte colony-stimulating factor (G-CSF) rapidly loses the biological activity and the receptor binding capacity following radioiodination. We have made a mutein of human G-CSF, KW-2228, in which Thr-1, Leu-3, Gly-4, Pro-5, and Cys-17 were respectively substituted with Ala, Thr, Tyr, Arg, and Ser; showed more potent G-CSF activity; and retained full biological activity and receptor binding capacity at least 2 weeks of radioiodination. G-CSF is an effective growth factor for the blasts of myeloid leukemia. Radioiodinated KW-2228 was prepared using solid-phase glucose oxidase-lactoperoxidase. Human leukemia cell lines and the blast cells from leukemia patients were examined for binding. High affinity binding sites were identified on myeloid cell lines and on the blasts obtained from acute myeloid leukemia patients. Scatchard analysis showed that a single binding site for G-CSF was observed (361-1688 receptors/cell; Kd 128-1400 pM). In contrast, specific binding of 125I-KW-2228 was not demonstrated on lymphoblastic cell lines or the blast cells of acute lymphoid leukemia or lymphoma. This difference was reflected in the effectiveness of G-CSF to stimulate colony formation in acute myeloid leukemia blasts, while G-CSF did not stimulate colony formation of the blast cells from acute lymphoid leukemia.
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PMID:Receptor binding of human granulocyte colony-stimulating factor to the blast cells of myeloid leukemia. 168 9

The Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), isolated from a feline fibrosarcoma, is a replication defective acute transforming feline retrovirus that originated by transduction of feline c-kit sequences with feline leukemia virus (FeLV). The v-kit sequences of the HZ4-FeSV, a segment of 1106 nucleotides, correspond to sequences of the cytoplasmic domain of the c-kit receptor kinase. The HZ4-FeSV is known to encode an 80-kilodalton protein with FeLV gag and kit determinants. The P80gag-kit protein and its associated activities from HZ4-FeSV-transformed mink cells were characterized. The P80gag-kit protein was found to be myristoylated, suggesting a membrane association for this protein. In agreement with the predicted relationship with tyrosine kinases, by using the in vitro immune complex-kinase procedure, the P80gag-kit protein was shown to display a tyrosine-specific autophosphorylation activity. In vivo, the P80 protein was found to be phosphorylated on serine and threonine and to a lesser degree on tyrosine. In addition, potential in vivo protein substrates for tyrosine-specific phosphorylation mediated by the P80gag-kit kinase were identified in HZ4-FeSV-transformed cells.
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PMID:Tyrosine protein kinase activity of the HZ4-feline sarcoma virus P80gag-kit-transforming protein. 169 69

In addition to the 85-95 kD CD44 species found on most hemopoietic cell types, the human myelomonocytic cell line KG1a expresses proteins of approximately 115 kD and 130 kD that react with monoclonal antibodies belonging to CD44. The possibility that these higher molecular weight species may represent novel CD44 isoforms containing additional protein sequence was investigated. CD44 cDNA clones were isolated from a plasmid-based expression library prepared from KG1a mRNA. One of the three clones obtained (clone 2.3) was found to encode a CD44 molecule of approximately 130 kD in transfected COS cells. Sequences analysis indicated that the molecule encoded by this cDNA clone, designated CD44R1, was essentially identical to CD44 except for the presence of an additional 132 amino acids inserted into the extracellular domain. This inserted region is rich in serine and threonine residues that may serve as sites of O-linked glycosylation, and contains a potential site of N-linked glycosylation and a potential site of chondroitin sulphate attachment. PCR analysis using primers that flank the inserted region present within CD44R1 identified an additional CD44 isoform, designated CD44R2, that contains only the last 69 amino acids present within the unique region of CD44R1. Peripheral blood mononuclear cells and granulocytes from normal individuals and patients with chronic myelogenous leukemia, polycythemia vera, or acute myelomonocytic leukemia, express both CD44R1 and CD44R2. In contrast, CD44R1 and CD44R2 appear to be differentially expressed in various CD44-positive cell lines. Thus KG1a, and the Epstein-Barr Virus-transformed B cell lines WalkDR4 and Way-1 express both CD44 and the CD44 isoforms CD44R1 and CD44R2, while the myeloid cell lines HL60 and U937 express high levels of CD44, but only very low levels of CD44R1 and CD44R2. The CD44-negative cell lines DHL-4, DHL-10, Jurkat, and K562 are also negative for CD44R1 and CD44R2.
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PMID:Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells. 205 74


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