Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0272170 (SDS)
 50,377 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

pp59v-rel exists in association with specific cellular proteins within lymphoid cells transformed by reticuloendotheliosis virus (REV-T). These include the cellular rel homolog (p75c-rel) as well as a 40-kDa avian homolog to I kappa B. The brief exposure of REV-T-transformed lymphoid cells to micromolar concentrations of ZnSO4 induces profound alterations within these protein complexes. Most of the constituents of the rel protein complexes (to include pp59v-rel, p75c-rel, and p115) translocate from the cytosol to the nucleus. This system has been used to characterize the molecular events that accompany the activation of rel protein complexes. The level of phosphorylation increases on three proteins within these complexes: pp59v-rel, p75-c-rel, and pp40. The degree of phosphorylation on pp59v-rel is such that its relative mass increases 3 to 6 kDa when resolved by SDS-polyacrylamide gel electrophoresis. pp59v-rel is phosphorylated on serine and threonine residues predominantly within a single domain of 17.5 kDa. Similarly, p75c-rel exhibits a corresponding increase in its relative mass with increased phosphorylation. The increased phosphorylation of pp40 is accompanied by its dissociation from the cytosolic rel protein complexes. These observations draw parallels with the induction of the NF-kappa B trans-activating factor.
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PMID:Alterations within pp59v-rel-containing protein complexes following the stimulation of REV-T-transformed lymphoid cells with zinc. 131 81

Nerve growth factor (NGF) binds to two structurally unrelated transmembrane proteins on the surface of PC-12 cells, a 75-kDa glycoprotein with a short cytoplasmic sequence, and the trk protooncogene (pp140c-trk), a protein tyrosine kinase activated by NGF. Immediately after binding to cells, NGF induces changes in serine/threonine phosphorylation of several proteins. We have explored the relative roles of these two NGF binding proteins in mediating the activation of two intracellular kinases that may be responsible for some of these phosphorylations. The raf-1 protooncogene is a serine/threonine kinase activated by several growth factors and oncogenic proteins. Treatment of PC-12 cells with NGF increases the serine and threonine phosphorylation of raf-1 in an anti-raf-1 immunoprecipitate kinase assay. This increased phosphorylation observed in vitro is dose-dependent and transient and is accompanied by the NGF-dependent shift in the mobility of immunoblotted raf-1 on SDS sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an effect thought to reflect phosphorylation. NGF-dependent activation of raf-1 is not dependent on protein kinase C, since prolonged exposure to phorbol esters under conditions that cause down-regulation of cellular protein kinase C activity has no effect on the NGF response. Expression of pp140c-trk in 3T3 fibroblasts (3T3-c-trk), as evidenced by cross-linking of 125I-NGF to the 140-kDa protein, permits the NGF-dependent activation of raf-1 kinase, detected in the immunoprecipitate kinase assay, anti-raf immunoblot shift on gel electrophoresis, and incorporation of [32P]orthophosphate into the raf-1 protein. The concentration dependence of raf-1 activation is identical in 3T3-c-trk and PC-12 cells, despite the absence of the 75-kDa NGF binding protein in 3T3-c-trk cells. NGF is without effect in untransfected 3T3 cells or in Chinese hamster ovary cells overexpressing p75, although raf-1 is present in these cells. Similarly, the NGF-dependent activation of mitogen-activated protein (MAP) kinase is detected in 3T3-c-trk cells, but not in untransfected 3T3 or Chinese hamster ovary cells overexpressing p75. As described for raf-1 activation, the NGF dose responses for MAP kinase activation in 3T3-c-trk and PC-12 cells are virtually superimposable. These data indicate that the activation of these two serine/threonine kinases by NGF is mediated solely by binding to and activating the pp140c-trk receptor.
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PMID:Nerve growth factor stimulates the activities of the raf-1 and the mitogen-activated protein kinases via the trk protooncogene. 132 11

We have compared the properties of a rat aorta-derived protein kinase C substrate (p75) with those of 80 kDa kinase C substrates from rat brain (MARCKS) and rabbit aorta (p80). Rat aortic p75 appeared to be closely related to rat brain MARCKS on the basis of: solubility in perchloric acid and trichloroacetic acid, heat stability, isoelectric point (pI approximately 4.2), overall V8 protease phosphopeptide map, and immunocrossreactivity with an antibody directed against the N-terminal domain of MARCKS. However, p75 could be distinguished from rat brain MARCKS and from the rabbit aorta-derived p80 on the basis of its consistently more rapid electrophoretic mobility in SDS-containing gels, and in terms of a unique proteolytic phosphopeptide found in MARCKS but not in aortic p75. We conclude that p75 probably belongs to the family of protein kinase C substrates represented by MARCKS, and that differences in post-translational processing (glycosylation) or mRNA processing may account for the unique properties of the p75 protein in rat aortic tissue.
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PMID:Comparison of an endogenous protein kinase C substrate in rat aorta with rat brain MARCKS. 133 18

Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. The monoclonal antibody MF1, which mediates clearance of peripheral microfilaremia in a gerbil infection model, recognizes two stage-specific proteins, p70 and p75, in B. malayi microfilariae. cDNA coding for the MF1 antigen was sequenced, and the predicted protein sequence shows significant similarities to chitinases from bacteria and yeast. When microfilarial extracts and purified preparations of the MF1 antigen were tested for chitinase activity, strong bands of chitin-degrading activity comigrated in SDS/PAGE with p70 and p75 and showed a reduction-dependent mobility shift characteristic of the MF1 antigen. Thus, the MF1 antigen is microfilarial chitinase, which may function to degrade chitin-containing structures in the microfilaria or in its mosquito vector during parasite development and transmission.
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PMID:Transmission-blocking antibodies recognize microfilarial chitinase in brugian lymphatic filariasis. 154 46

MYB gene products are thought to be regulators of cellular replication and of differentiation. The major product of the avian MYB gene is a 75 kDa nuclear phosphoprotein which can activate transcription. A minor 89 kDa MYB protein of unknown function has also been described in murine and human cells. Additional heterogeneity at the level of MYB RNA which could affect the structure of MYB proteins has been described in several species. Such heterogeneity could explain the diverse effects of the MYB gene. To investigate the possible existence of heterogeneous and/or cell lineage-specific MYB proteins, five different avian hematopoietic tissues (bone marrow, bursa of Fabricius, embryonic spleen, thymus and yolk sac) were examined by immunoprecipitation with several MYB-specific antisera and SDS-PAGE analysis. In all five tissues there was a 75 kDa protein of uniform size which varied in abundance in a tissue-specific manner paralleling that observed for the 4.0 kb MYB RNA. A less abundant 89 kDa protein was also detected by several antisera in bone marrow, spleen, thymus and yolk sac but not in bursa. This 89 kDa MYB protein appears to be analogous to the 89 kDa MYB protein encoded by a minor but larger (360 nucleotides) MYB mRNA in murine and human cells. Immunoprecipitation of MYB proteins with an antiserum specific for exons 8 and 9 revealed a 74 kDa protein which co-precipitated and appeared to be complexed with p75 in normal hematopoietic cells and with the 48 kDa product of v-myb in leukemic cells.
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PMID:Expression of MYB proteins in avian hematopoietic tissues. 192 15

A xenoantiserum raised in rabbits by immunization with strain 13 guinea-pig antigen-activated T-lymphocytes was previously found to recognize a non-immunoglobulin, 75,000 mol. wt glycoprotein synthesized by guinea-pig T-cells. This protein, p75, has been further characterized to determine its biochemical properties and its expression by various cell types. p75 was found to be a single-chain protein which could be bound by the lectin Lens culinaris hemagglutinin. It has an apparent mol. wt slightly greater than mu-chain as assessed by SDS-polyacrylamide gel electrophoresis and could not be precipitated by anti-guinea-pig immunoglobulin reagents. It exhibited considerable charge heterogeneity during isoelectric focusing and was not affected by neuraminidase treatment, p75 was synthesized by thymus, spleen and lymph node cells, by antigen-stimulated T-cells from strain 13 and strain 2 guinea-pigs, and by guinea-pig B-cell L2C leukemia lines, but not by normal B-lymphocytes or macrophages. No differences between the isoelectric focusing patterns of p75 molecules isolated from different cell types could be demonstrated. The chemical properties of p75 and its expression by the cell types so far examined indicate that p75 is a possible candidate for the guinea-pig homologue of the murine Lyt-1 antigen.
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PMID:Characterization of a 75,000 mol. wt glycoprotein synthesized by guinea-pig T-lymphocytes: a possible homologue of Lyt-1 antigen. 698 89

Human urine is known to contain a 30 kDa soluble form of the p75-TNF receptor (sTNF-R2). In this work we have purified sTNF-R2 from the urine of normal subjects and further characterized its structure and activity. sTNF-R2 was resolved by reducing SDS-PAGE in a major band of 30 kDa, similar in size to the previously described urinary sTNFR2, and in a minor band of 45 kDa. "Western" blotting analysis with anti-TNF-R1 and anti-TNF-R2 antibodies showed that both bands were immunologically related to the membrane TNF-R2. Glycosylation studies indicated that the 30 kDa is N-glycosylated while the 45 kDa form is N- and O-glycosylated, and suggested that both forms contain terminally linked sialic acid that is differentially recognized by lectins. These results indicate that human urine contains, besides the 30 kDa form, a new form of 45 kDa characterized by different glycosylation type and degree.
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PMID:Identification of differentially glycosylated forms of the soluble p75 tumor necrosis factor (TNF) receptor in human urine. 779 72

Two soluble tumour-necrosis-factor-alpha(TNF)-binding proteins are derived from the extracellular domains of the p55 and p75 TNF receptors. They are considered to play a pivotal regulatory role in TNF-mediated inflammatory processes, including diseases such as rheumatoid arthritis, by competing with the cell surface receptors for TNF and lymphotoxin (LT, tumour-necrosis factor beta). The extracellular domains of the two receptors each contain four similar cysteine-rich repeats of about 40 amino acids, in common with several other cell surface proteins including the p75 nerve-growth-factor receptor and the CD40 and Fas antigens. The aim of this study was to characterize the involvement of the four cysteine-rich repeats of the human p55 TNF receptor in TNF and LT binding by both membrane-bound and soluble forms of the receptor. Individual repeats were systematically deleted by PCR mutagenesis and the variants transiently expressed in COS cells. Immunoprecipitated receptor variants exhibited the expected sizes on SDS/PAGE gels, and bound a panel of conformation-dependent anti-(TNF receptor) antibodies. Binding of TNF by the four soluble derivatives was compared with binding by the wild-type soluble receptor using a TNF-affinity column and a BIAcore Biosensor, by measurement of their ability to inhibit TNF cytotoxicity on WEHI cells, and 125I-TNF binding to U937 cells. delta 4, which lacks the fourth cysteine-rich repeat, bound TNF comparably with the full-length soluble receptor. TNF-binding affinity was unaltered by deletion of the fourth membrane-proximal cysteine-rich repeat, as determined by Scatchard analysis of the transmembrane derivatives. We conclude that the fourth cysteine-rich repeat is not required for TNF binding. In contrast, both the soluble and the transmembrane derivatives lacking any one of the first, second or third repeats failed to bind TNF. Although we cannot entirely exclude the possibility that this may be due to indirect conformational change, rather than the removal of essential epitopes, our results suggest that the first three repeats are each required for TNF binding by both the soluble and the cell-surface receptor.
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PMID:Characterization of ligand binding by the human p55 tumour-necrosis-factor receptor. Involvement of individual cysteine-rich repeats. 805 60

An expression plasmid encoding the extracellular domain of the 75-kDa human tumor necrosis factor (TNF) type 2 receptor (TNF-R2) was constructed and used to generate a stable cell line secreting soluble TNF-R2 (sTNF-R2). Purified sTNF-R2 was resolved by SDS-PAGE into one band of approximate M(r) 43,000, consistent with a molecular weight of 36,000 +/- 4800 obtained by sedimentation equilibrium analysis. The apparent molecular weight observed by gel filtration chromatography was approximately 136,000. Glycosylation analysis revealed that Asn-149 is fully glycosylated, while Asn-171 is incompletely glycosylated (approximately 50%), and that a proline-, serine-, and threonine-rich region (residues 175-234) contains O-linked carbohydrate structures. Scatchard analysis of [125I]TNF-alpha and [125I]TNF-beta binding to sTNF-R2 gave dissociation constants (Kd) of 0.3 and 0.75 nM, respectively, comparable to those observed for intact cell-surface TNF-R2. The sTNF-R2 was found to block the cytotoxicity of both TNF-alpha and TNF-beta in a murine L-M cell assay. The sizes of the sTNF-R2.TNF-alpha and sTNF-R2.TNF-beta complexes determined by gel filtration chromatography were approximately 322 and 204 kDa, respectively. The stoichiometry of the sTNF-R2.TNF-alpha and sTNF-R2.TNF-beta complexes were examined by size-exclusion chromatography, sedimentation equilibrium, and cross-linking. The data from these studies suggest that at least two molecules of sTNF-R2 can bind to a single TNF-alpha or TNF-beta trimer.
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PMID:Biochemical characterization of the extracellular domain of the 75-kilodalton tumor necrosis factor receptor. 838 89

The structure and the activity of urinary soluble TNF receptor type 1 (sTNF-R1), isolated from the urine of normal individuals, has been characterized and compared with that of recombinant sTNF-R1 expressed in CHO cells and with that of a nonglycosylated form expressed in Escherichia coli. Urinary sTNF-R1 was resolved in a major band of 31-33 kD and in a 48 kD band (less than 5% of total) by reducing SDS-PAGE; CHO sTNF-R1 was resolved in two bands of 29 and 31 kD. All bands were recognized by various anti-sTNF-R1 antibodies as well as by TNF-alpha in western and ligand blotting assays. No cross-reaction was observed with anti-TNF-R2 antibodies. N- and O-glycosylation studies indicated that (1) the 29-31 kD recombinant form as well as the 31-33 kD urinary form are N-glycosylated; (2) the differences between the 29-31 and 31-33 kD recombinant and natural products are mainly related to differences in the N-linked sugar content; and (3) the 48 kD sTNF-R1 isolated from urine also contains O-linked sugars. The urinary sTNF-R1 antigen mixture was able to inhibit TNF-alpha cytotoxicity with a potency comparable to that of nonglycosylated E. coli sTNF-R1. At variance, urinary sTNF-R1 was able to inhibit TNF-beta sevenfold more efficiently than E. coli sTNF-R1. In conclusion, two subtypes of sTNF-R1 have been isolated from urine: a main N-glycosylated form of 31-33 kD and a N- and O-glycosylated form of 48 kD that appears to be a minor constituent of the urinary sTNF-R1 antigen.
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PMID:Identification of two forms (31-33 and 48 kD) of the urinary soluble p55 tumor necrosis factor receptor that are differentially N- and O-glycosylated. 859 Mar 18


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