Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obvious protection of the catalytic activity of Esch. coli L-asparaginase by alpha 2-macroglobulin (alpha 2M) was observed under conditions otherwise propitious to the dissociation of the tetrameric molecule into inactive subunits, i.e. very diluted enzyme solutions or the presence of either SDS or urea. The degree of protection depended on enzyme and alpha 2M concentrations respectively, and on the preincubation time of the alpha 2M-enzyme mixture prior to substrate addition. The formation of a catalytically active complex between alpha 2M and L-asparaginase was confirmed by gel filtration on a Sephadex-G column and by polyacrylamide gel electrophoresis. The fact that the migration distance of the active complex corresponded to the migration of alpha 2M and the absence in that case of a migration band corresponding to the intact molecule suggest that complexing of the enzyme with alpha 2M prevented its dissociation into subunits and thus its inactivation. Addition of alpha 2M to the already dissociated enzyme molecule did not restore its catalytic activity. Alpha2-macroglobulin was shown to have an inhibiting effect on the proteolytic activity of almost all proteases and no effect on their esterolytic activity. Furthermore, it prevents the inhibition of esterolytic activity by some natural compounds. The effect of alpha 2M on other types of catalytic activity has not been investigated enough to afford a generalization of the possible role of this macroglobulin in the control of enzyme activity in the body. This paper reports the results of an in vitro study of the effect of alpha 2M on the catalytic activity of an important amidase, i.e. L-asparaginase (L-asparagine amidohydrolase 3.5.1.1), which in recent years has been used in the treatment of acute lymphocytic leukemia in children.
Mol Cell Biochem 1979 Feb 09
PMID:Interaction of alpha 2-macroglobulin with L-asparaginase. 9 Mar 34

1. Rabbits were actively immunized aganist angiotensin II (AII). 2. Basal plasma aldosterone concentration was 0-058 plus or minus 0-027 pmol/ml (20-7 plus or minus 9-6 pg/ml) (mean plus or minus SD) in immunized and 0-056 plus or minus 0-021 pmol/ml (20-2 plus or minus 7-5 pe. When the endogenous formation of AII was stimulated by frusemide, by haemorrhage or by feeding with low sodium diet, a significant increase of plasma aldosterone was observed with no difference between immunized and non-immunized animals. 3. In non-immune rabbits, the average mean arterial blood pressure rose 13 mmgHg during the infusion of AII (5 pmol min--1 kg-1) and 27 mmHg during the infusion of 50 pmol min-1 kg-1. In contrast, there was no clear increase in blood pressure in the immunized animals. The blood pressure rose in immune animals (15 mmHg) and in non-immune animals (36 mmHg) during the infusion of 200 pmol min-1 kg-1 ALL. Plasma aldosterone rose in all animals in response to each of the three infusions with no significant difference between the two groups. 4. It is concluded that the immunization against ALL blocked only the pressor effect of the peptide but had no clear influence on the response of plasma aldosterone to increased ALL. Differences between the affinities of the adrenal and vascular AII receptors may explain these findings.
Clin Sci Mol Med 1975 May
PMID:Effect of immunization against angiotensin II on blood pressure and on plasma aldosterone in the rabbit. 112 32

A highly malignant human T-cell receptor (TCR) gamma/delta+ T-cell leukemia was shown to have a productive rearrangement of the TCR delta locus on one chromosome 14 and a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on the other chromosome 14. Chromosome walking coupled with pulsed-field gel electrophoretic (PFGE) analysis determined that the TCR J delta 1 gene fragment of the involved chromosome was relocated approximately 280 kb downstream of the c-myc proto-oncogene locus found on chromosome band 8q24. This rearrangement was reminiscent of the Burkitt's lymphoma variants that translocate to a region identified as the pvt-1 locus. Sequence comparison of the breakpoint junctions of interchromosomal rearrangements in T-cell leukemias involving the TCR delta-chain locus revealed novel signal-like sequence motifs, GCAGA(A/T)C and CCCA(C/G)GAC. These sequences were found on chromosome 8 at the 5' flanking site of the breakpoint junction of chromosome 8 in the TCR gamma/delta leukemic cells reported here and also on chromosome 1 in T-cell acute lymphocytic leukemia patients carrying the t(1;14)(p32;q11) rearrangement. These results suggest that (i) during early stages of gamma delta T-cell ontogeny, the region 280 kb 3' of the c-myc proto-oncogene on chromosome 8 is fragile and accessible to the lymphoid recombination machinery and (ii) rearrangements to both 8q24 and 1p32 may be governed by novel sequence motifs and be subject to common enzymatic mechanisms.
Mol Cell Biol 1992 Oct
PMID:Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation. 140 58

Previous studies have documented the metabolism of a broad range of folate antimetabolites to polyglutamate derivatives by the enzyme folylpoly-gamma-glutamate synthetase (FPGS). The activity of the more recently developed classes of antifolates directed against thymidylate synthase and de novo purine synthesis is sufficiently dependent on polyglutamation that these compounds should be specifically cytotoxic to any normal or malignant proliferating cell expressing this enzyme. We have studied the patterns of expression of FPGS in mammalian cells and tissues during rapid growth, growth arrest, differentiation, and embryonic development. During embryogenesis in the rat, FPGS levels in liver and brain were higher during the period of proliferative activity and then dropped to a level characteristic of the adult organs. However, the levels in liver were substantially higher than those in brain at any given time. This pattern was mimicked in mouse C3H 10T1/2 embryo fibroblast cells, in which FPGS activity decreased after cessation of growth but then remained at a lower steady state level during an extended period of postconfluent culture. Enzyme activity also dropped after the differentiation of human HL-60 promyelocytic leukemia cells. In a human homolog of these experimental systems, FPGS levels were below the limits of detection in circulating mature human hematopoietic cells of the granulocytic, lymphoblastic, and erythrocytic lineages. In striking contrast, substantial levels of FPGS were found in circulating lymphoblasts from eight patients with acute lymphoblastic leukemia. The levels of FPGS found in these transformed stem cells would help to explain the sensitivity of many acute lymphoblastic leukemias to folate antimetabolites. We concluded that expression of FPGS is regulated by at least two mechanisms, one of which is linked to proliferation and the other of which controls enzyme levels after differentiation and is tissue specific.
Mol Pharmacol 1992 Oct
PMID:Determinants of antifolate cytotoxicity: folylpolyglutamate synthetase activity during cellular proliferation and development. 143 44

Chronic myelogenous leukemia and one type of acute lymphoblastic leukemia are characterized by a 9;22 chronosome translocation in which 5' sequences of the bcr gene become fused to the c-abl proto-oncogene. The resulting chimeric genes encode bcr/abl fusion proteins which have deregulated tyrosine kinase activity and appear to play an important role in induction of these leukemias. A series of bcr/abl genes were constructed in which nested deletions of the bcr gene were fused to the c-abl gene. The fusion proteins encoded by these genes were assayed for autophosphorylation in vivo and for differences in subcellular localization. Our results demonstrate that bcr sequences activate two functions of c-abl; the tyrosine kinase activity and a previously undescribed microfilament-binding function. Two regions of bcr which activate these functions to different degrees have been mapped: amino acids 1 to 63 were strongly activating and amino acids 64 to 509 were weakly activating. The tyrosine kinase and microfilament-binding functions were not interdependent, as a kinase defective bcr/abl mutant still associated with actin filaments and a bcr/abl mutant lacking actin association still had deregulated kinase activity. Modification of actin filament functions by the bcr/abl tyrosine kinase may be an important event in leukemogenesis.
Mol Cell Biol 1991 Mar
PMID:Activation of tyrosinase kinase and microfilament-binding functions of c-abl by bcr sequences in bcr/abl fusion proteins. 170 8

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.
Mol Cell Biol 1992 Feb
PMID:Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. 173 48

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.
Mol Cell Biol 1991 Sep
PMID:Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. 187 48

A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was established from the bone marrow of a patient with non-T-ALL. The HBL-3 cell line expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface immunoglobulin (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked the common acute lymphoblastic leukemia antigen (CALLA) and antigenic markers characteristic of T-cell and myeloid cell lineages. The HBL-3 cells had structural rearrangements of both the homologous chromosome 9s, including a translocation with chromosome 1 which has been reported in a patient with common ALL. The cell line had rearranged immunoglobulin heavy chain genes but retained germ-line kappa light chain genes and germ-line T-cell receptor beta- and gamma-chain genes. The HBL-3 cell line was strongly positive for terminal deoxynucleotidyl transferase (TdT). These findings indicate that the HBL-3 cell line is derived from the earliest B-cell committed to B-cell lineage.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:A newly established human acute lymphoblastic leukemia cell line with characteristics of the earliest B-cell maturation. 197 32

The p85 glycoprotein expressed on a variety of human cell types including astrocytes and lymphocytes has not been associated with the CD44 cluster. The recent demonstration that Hermes, a glycoprotein implicated in the adhesion of lymphocytes to endothelium, belongs to the CD44 cluster raises interesting questions concerning the role of this molecule on astrocytes and on non-lymphoid cells. To obtain confirmation of the identity of p85 glycoprotein and CD44, p85 glycoprotein was purified from B-chronic lymphocytic leukemia cells by affinity to monolonal 50B4-IgG and electrophoretic elution, digested with trypsin or CNBr and fractionated by reversed-phase HPLC. The sequences of three peptides were obtained which could be aligned with the amino acid sequence deduced from the CD44 cDNA at residues 49-54, 59-66 and 309-323. These constitute the first reported peptide sequences for antigens of the CD44 cluster and confirm that p85 glycoprotein is indeed the product of the CD44 gene. Since two different cDNA clones encoding molecules with cytoplasmic tails of 72 and 5 amino acids have been isolated, the isolation of peptide 309-323 confirms the existence of a processed protein with the longer cytoplasmic domain. Using a cDNA probe, we have characterized the expression of CD44 in several normal and malignant cell types. The level of CD44 mRNA was correlated with the surface expression of CD44 antigens (50B4) in several leukemic cell lines, in astrocytoma lines and in normal granulocytes. Negative cells included the Y79 retinoblastoma line, the NALM-6 leukemic line and endothelial cells. Identical mRNA species of 5.0, 2.3 and 1.7 kb were present in all CD44-positive samples, including normal granulocytes, astrocytoma, melanoma and leukemia cell lines and leukemic cells from patients. The highest level of expression of CD44 was observed on astrocytoma lines and on acute lymphoblastic leukemia cells of immature phenotype. The presence of high levels of CD44 on malignant cells could increase the ability of these cells to adhere to matrix proteins and/or to interact with endothelium, thus potentially altering their capacity for invasiveness and metastasis.
Mol Immunol 1990 Oct
PMID:Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein. 223 56

We have isolated the gene for a novel growth regulator, amphiregulin (AR), that is evolutionarily related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). AR is a bifunctional growth modulator: it interacts with the EGF/TGF-alpha receptor to promote the growth of normal epithelial cells and inhibits the growth of certain aggressive carcinoma cell lines. The 84-amino-acid mature protein is embedded within a 252-amino-acid transmembrane precursor, an organization similar to that of the TGF-alpha precursor. Human placenta and ovaries were found to express significant amounts of the 1.4-kilobase AR transcript, implicating AR in the regulation of normal cell growth. In addition, the AR gene was localized to chromosomal region 4q13-4q21, a common breakpoint for acute lymphoblastic leukemia.
Mol Cell Biol 1990 May
PMID:The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. 232 43


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