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)

The GATA-1 and GATA-2 transcription factors, which each contain two homologous zinc fingers, are important hematopoietic regulators expressed within the erythroid, mast cell, and megakaryocytic lineages. Enforced expression of either factor in the primitive myeloid line 416B induces megakaryocytic differentiation. The features of their structure required for this activity have been explored. The ability of 12 GATA-1 mutants to promote 416B maturation was compared with their DNA-binding activity and transactivation potential. Differentiation did not require any of the seven serine residues that are phosphorylated in vivo, an N-terminal region bearing the major transactivation domain, or a C-terminal segment beyond the fingers. Removal of a consensus nuclear localization signal following the second finger did not block differentiation or nuclear translocation. The N-terminal finger was also dispensable, although its removal attenuated differentiation. In contrast, the C-terminal finger was essential, underscoring its distinct function. Remarkably, only 69 residues spanning the C-terminal finger were required to induce limited megakaryocytic differentiation. Analysis of three GATA-2 mutants led to the same conclusion. Endogenous GATA-1 mRNA was induced by most mutants and may contribute to differentiation. Because the GATA-1 C-terminal finger could bind its target site but not transactivate a minimal reporter, it may direct megakaryocytic maturation by derepressing specific genes and/or by interacting with another protein which provides the transactivation function.
Mol Cell Biol 1995 Feb
PMID:The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. 782 32

The effect of terbium (Tb) on the protease activity in pancreas of mice was studied. Administration of Tb at doses of 20 and 200 mumol/kg increased the activities of trypsin and carboxypeptidase A, but did not affect the activities of chymotrypsin and carboxypeptidase B. High Tb concentrations were found in the liver and spleen compared to the kidney and pancreas. Increases in Ca concentrations in the pancreas, kidney, and spleen after Tb administration were observed. The pancreatic slice experiments showed the increase in trypsin activity after Tb treatment and increases in trypsin and carboxypeptidase A after Ca treatment. Tb inhibited strongly the activities of authentic chymotrypsin and carboxypeptidase A. These results suggest that the increase in trypsin activity in the pancreas after Tb administration results from the activation of trypsinogen by Tb and Ca ions and that the increase in carboxypeptidase A activity is due to the activation of procarboxypeptidase A by trypsin and Ca ion, which increased after Tb administration.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Effect of terbium on protease activity in pancreas of mice. 799 67

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.
Mol Cell Biol 1994 May
PMID:Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells. 816 66

The rat A3 adenosine receptor (AR) is a recently characterized AR subtype cloned from testis and brain cDNA libraries. N6-2-(4-Amino-3-[125I]iodophenyl)ethyladenosine, a high affinity A1AR agonist, has served as the only radioligand available for study of the A3AR. The relatively low affinity of N6-2-(4-amino-3-[125I] iodophenyl)ethyladenosine for the A3AR and its greater A1AR selectivity necessitate the development of more appropriate radioligands for A3AR analysis. This report characterizes 125I-4-aminobenzyl-5'-N-methylcarboxamidoadenosine (125I-AB-MECA), a high affinity radioligand for the A3AR, in two cell lines that express this AR subtype. Membranes from Chinese hamster ovary (CHO) cells expressing the rat A3AR and from the rat mast cell line RBL-2H3 bound 125I-AB-MECA with Kd values of 1.48 +/- 0.33 nM and 3.61 +/- 0.30 nM, respectively. As determined by 125I-AB-MECA binding, levels of A3AR expression in the A3AR-CHO cell line and RBL-2H3 cells were 3.06 +/- 0.21 pmol/mg and 1.02 +/- 0.13 pmol/mg, respectively. Binding of 125I-AB-MECA was characterized in competition assays. In the A3AR-CHO cell line a potency order of cyclohexyl-5'-N-ethylcarboxamidoadenosine (cyclohexyl-NECA) = benzyl-NECA > (-)-N6-[(R)-phenylisopropyl]adenosine = NECA was observed, and in RBL-2H3 cells (-)-N6-[(R)-phenylisopropyl]adenosine and NECA were equipotent. Xanthine amine congener (XAC) and 8-cyclopentyl-1,3-dipropylxanthine did not significantly inhibit 125I-AB-MECA binding. The parent compound, AB-MECA, dose-dependently inhibited forskolin-stimulated adenylyl cyclase activity in A3AR-CHO cell membranes. 125I-AB-MECA bound to the rat A1AR and canine A2aAR expressed in COS-7 cells with Kd values of 3.42 +/- 0.43 nM and 25.1 +/- 12.6 nM, respectively. This binding was significantly reduced in the presence of 1 microM XAC. In RBL-2H3 cells, XAC had no effect on 125I-AB-MECA affinity and reduced the level of radioligand binding by approximately 5%.
Mol Pharmacol 1994 May
PMID:125I-4-aminobenzyl-5'-N-methylcarboxamidoadenosine, a high affinity radioligand for the rat A3 adenosine receptor. 819 Jan 12

Silicosis provides a good model for chronic interstitial pulmonary inflammation. In order to clarify the role of mast cells in the development of interstitial lung diseases, silica suspension was transnasally administered to mast cell-deficient mice (WBB6F1-W/Wv) and their mast cell-intact littermates (WBB6F1(-)+/+) as well as to normal mice (C57BL/6). Histologic examinations and analyses of bronchoalveolar lavage fluid (BALF) components indicated that silica instillation induces less severe lung lesions in mast cell-deficient mice than in mast cell-intact mice. BALF neutrophilia was prominent in mast cell-intact mice, but mast cell-deficient mice developed significantly milder BALF neutrophilia. An increase in the number of lung mast cells was observed in mast cell-intact mice. To further prove the involvement of mast cells, bone marrow-derived cultured mast cells from +/+ mice were adoptively transferred to mast cell-deficient mice. These mast cell-reconstituted mice developed more severe pulmonary lesions than did the mast cell-deficient mice; the severity of the lesions was similar to that in mast cell-intact mice. In addition, BALF neutrophilia was elicited by mast cell reconstitution. A significant number of mast cells was found in the lungs of mast cell-reconstituted mice when silica was administered. These results suggest the involvement of mast cells in the development of silicosis and implicate interactions between mast cells and neutrophils in the pathogenesis of this disorder.
Am J Respir Cell Mol Biol 1993 Nov
PMID:Mast cells are essential for the full development of silica-induced pulmonary inflammation: a study with mast cell-deficient mice. 821 87

The effect of lysosomal storage diseases on the ultrastructure of human mast cells has not previously been reported. Indeed, there has been little published evidence indicating that mast cells contain typical lysosomes. However, mast cell cytoplasmic granules contain hydrolases similar to those found in lysosomes, but which differ from lysosomal hydrolases in exhibiting optimal activity at higher pH. We therefore examined by transmission electron microscopy the dermal mast cells in 58 biopsies of patients exhibiting 1 of 29 different lysosomal storage diseases. We found mast cells containing abnormal lysosomes in 16 of these disorders. In 6 of these 16 diseases, the mast cells' cytoplasmic granules appeared normal. These observations indicate that human mast cells can contain lysosomes, and provide evidence that the enzymes affected by lysosomal storage diseases are active in mast cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Ultrastructure of human dermal mast cells in 29 different lysosomal storage diseases. 822 Aug 22

The proteolytic enzyme, chymase, was used to identify mast cells in rat gastrocnemius muscles which were crush-injured or incised in order to determine if mast cells exhibited proliferation and degranulation. Some of the crush-injured rats were subjected to 0 g for 14 days after injury on the Cosmos 2044 satellite to study the effects of weightlessness on the mast cell response. A variety of ground-based injured models were used, including a group of hindlimb-unloaded animals acting as controls and testing the suitability of the hindlimb-unloaded animal as a model for muscle healing during weightlessness. In most cases, the numbers of mast cells and their apparent size increased after injury. When mast cell degranulation was evident, the granules containing chymase often were free in the loose connective tissue and along the edge of myofibers. The mast cell response was most exaggerated in animals subjected to 0 g and least visible in the hindlimb-unloaded ones. Thus, gravitational stress may influence mast cell physiology and the hindlimb-unloaded animal may not be a good model for investigating muscle healing.
Exp Mol Pathol 1993 Oct
PMID:Effect of injury on mast cells of rat gastrocnemius muscle with respect to gravitational exposure. 822 16

We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction profile of marker genes for primitive endoderm (collagen alpha IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and IL-11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.
Mol Cell Biol 1993 Jan
PMID:Hematopoietic commitment during embryonic stem cell differentiation in culture. 841 45

Immunohistology and in situ hybridization were used to evaluate the presence, activation status, and cytokine mRNA profile of cells in the bronchial mucosa during human allergen-induced asthma. Fifteen atopic asthmatic subjects underwent inhalation challenge with allergen and with allergen diluent, performed in random order separated by an interval of at least 3 wk. Bronchial biopsies were obtained 24 h after challenge. Immunostaining revealed increases in the numbers of secreting eosinophils (EG2+; P < 0.05) and in interleukin-2 receptor (IL-2R)-positive cells (CD25+; P < 0.01) after allergen compared with diluent challenge. No differences were observed in the numbers of total leukocytes (CD45+), T lymphocytes (CD3+, CD4+, and CD8+), elastase-positive neutrophils, macrophages (CD68+), or mast cell subtypes (MCT+ or MCTC+). In situ hybridization revealed significant increases in the numbers of cells expressing mRNA for IL-5 (P < 0.02) and granulocyte/macrophage colony-stimulating factor (P < 0.01) after allergen compared with diluent challenge. A significant inverse relationship was observed between the number of cells expressing mRNA for IL-4 and for interferon-gamma (r = -0.75, P < 0.02). The results support the view that cytokines possibly from activated T lymphocytes may contribute to local eosinophil accumulation during allergen-induced asthma.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. 841 55

To enhance the already high quality of diffraction data for crystals of the hydrophobic protein crambin, X-ray data were collected at 130 K by the method of H. Hope to 0.83 A resolution. Refinement with PROLSQ yields a model with an R value of 10.5%. The final model had three parameter anisotropic vibration factors for all atoms, which included 367 protein heavy atoms, 372 hydrogen atoms and 144 solvent atoms with one ethanol molecule. Dihedral angles and hydrogen-bonding distances generally agree with earlier studies of high-resolution protein structures, but some new patterns are noted. Solvent-related helix distortions are reminiscent of those described by others. Helix and beta-sheet regions show distinct patterns in their side-chain conformations. Despite crambin's hydrophobic nature, its accessible surface area in the crystal is surprisingly close to that of water-soluble proteins like myoglobin and carboxypeptidase A. More of crambin's hydrophobic surface is buried in the crystal, perhaps accounting for its high order of diffraction. A total of 24% of the 46 residues show discrete disorder at 130 K. This includes five side-chains at both 300 and 130 K, and six more side-chains and an ethanol molecule at 130 K. Disorder is associated with the sequence microheterogeneity at Pro/Ser22 and Leu/Ile25, with space filling or with solvent disorder. Correlated conformations extend over three to five residues. The patterns of disorder in this structure reveal important principles of protein structure and its dynamics. Finding disordered groups correlated over 5 to 8 A suggests that co-ordinated motion extends in groups rather than simply as uncorrelated movement around an atom center. Thermal diffuse scattering experiments on insulin and lysozyme are consistent with this interpretation. Nearly all of the protein-bound solvent has been located. Less than 1% of protein accessible surface area remains uncovered by solvent or crystal contacts. Preliminary analysis of the solvent network reveals two main networks in each of four solvent regions.
J Mol Biol 1993 Mar 05
PMID:Atomic resolution (0.83 A) crystal structure of the hydrophobic protein crambin at 130 K. 845 May 43


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