Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of a 34-kDa (mol. wt.) acylpoly(1,3)galactoside (APG) extracted from a membrane proteoglycan of Klebsiella pneumoniae to human blood leucocytes was investigated. APG is made of a long poly(1,3)galactose chain, a core-like region and a lipid moiety which comprises two glucosamine residues bound to a phosphate group and two beta OH myristic acids. Fluoresceinated APG was shown to bind preferentially to monocytes and to a lesser extent to polymorphonuclear neutrophils, as determined by flow cytometry. Binding of fluoresceinated APG was inhibited by unlabelled APG; it was concentration dependent, but not saturable, with rapid kinetics. It occurred at +4 degrees C but was markedly increased at 37 degrees C. It involved trypsin-sensitive molecules on the membrane of monocytes. Neither the parent proteoglycan nor lipopolysaccharide from K. pneumoniae or Salmonella minnesota competed for APG binding. A minor non-specific binding to lymphocytes, occurring predominantly on B cells, was observed. Unlike that of lipopolysaccharide, the APG binding was not blocked by polymyxin B sulphate. Interaction between the galactose chain of APG and the galactose receptor does not account for the binding of APG to monocytes because the galactose receptor (Mac-2) is expressed at high density on activated macrophages but not on monocytes. Despite its strong binding to human blood monocytes, APG displayed a much weaker activity than K. pneumoniae membrane proteoglycan with respect to induction of monocyte cytokine synthesis. When administered as a Technetium 99 conjugate, APG was shown to label inflammatory foci in experimental animals, and its property as a marker of macrophages is currently being evaluated in clinical trials.
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PMID:Binding of a bacterial acylpoly(1,3)galactoside to human blood leucocytes. 161 80

During the last 15 years we have developed two biological systems, with whom it was possible to study the Ca++-dependent and the Ca++-independent adhesion on cellular level. In contrast to cells from other multicellular organisms, cells from the marine sponge Geodia cydonium are provided with Ca++-dependent adhesion mechanisms only. Two different mechanisms have been discovered by us, which were termed primary aggregation and secondary aggregation. In previous reports, we described that two macromolecules (aggregation factor [sAF] and aggregation receptor [AR] are involved in the secondary aggregation of sponge cells. The sAF was bound to a high-molecular-weight particle and was termed aggregation complex. The aggregation complex was shown to consist of two further functional subunits: UDP-glucuronosyltransferase and UDP-beta-D-galactosyltransferase. The AR with a molecular weight of approximately 17,000 was found to be a glycoprotein with D-glucuronic acid as the terminal sugar moiety. Data are presented from in vitro and in vivo experiments with the Geodia system, indicating that cell aggregation and cell separation are controlled first by alteration of the binding capacity of the aggregation receptor and second by an additional molecule (anti-aggregation receptor), which can decrease the interaction between the aggregation factor and the aggregation receptor. Recently we succeeded in the identification and isolation of the primary aggregation factor (pAF) from the same sponge species. This pAF is a glycoprotein that is firmly associated with the cell membrane. The Mr of the native pAF was 36,000; under denatured conditions three protein species were identified in the pAF preparation. We hypothesize that in contrast to the secondary aggregation, the initial aggregation of Geodia cells is mediated by the one-component system, the bivalent and bifunctional pAF. We were also able to dissociate the coral Eunicella cavolinii into single cells. These cells readily formed aggregates of a size of 2,100 micron during incubation in roller tubes: no aggregate formation was observed in non-rotating petri dishes. The formation of aggregates was not influenced by Ca++, urea or trypsin; it was also independent on temperature (4 degrees C to 30 degrees C) and pH (5.5-9.0). The intercellular material of the gorgonian contains a galactose-specific lectin, as determined by double diffusion experiments and haemagglutination inhibition experiments using a series of galacto-glycoconjugates. This lectin converted the aggregation-susceptible cells to aggregation-deficient cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The molecular mechanisms of the distinct calcium-dependent aggregation systems in marine sponges and corals. 286 62

A galactoside-binding lectin (hL-31) containing a collagen-like sequence was identified in human tumor cells. It was found to be the homologue of the IgE-binding protein, the macrophage cell-surface Mac-2 antigen, and the murine CBP35, RL-29, and mL-34 lectins. Here we report on the expression in Escherichia coli and functional analysis of recombinant hL-31 (rhL-31). The rhL-31 was purified in one step through an asialofetuin affinity column. The rhL-31 was reactive to anti-lectin antibodies and retained its lactose-dependent hemagglutination of trypsin-treated glutaraldehyde-fixed rabbit erythrocytes. The rhL-31 elutes from an affinity column as a 31-kDa monomer and undergoes homodimerization at relatively high protein concentrations, comparable to those used to mediate hemagglutination. Electron microscopy showed that the rhL-31 appears as a Y-shaped structure. Lactoperoxidase-catalyzed iodination of murine tumor cell-surface proteins followed by collagenase treatment revealed that the lectin is probably a peripheral membrane protein whereby both the amino and the carboxy termini are exposed on the outer cell membrane. These results point to the membrane disposition and orientation of the lectin and suggest a mechanism for a structure-function relationship of lectin activity.
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PMID:Structure-function relationship of a recombinant human galactoside-binding protein. 847 70

Mac-2-binding protein (M2BP) is a secreted glycoprotein suggested to have a role in host defense. It forms linear and ring-shaped oligomers, with each ring segment being composed of two monomers. We have produced recombinant human M2BP fragments comprising domains 1 and 2 (M2BP-1,2) and domains 3 and 4 (M2BP-3,4) in 293 human kidney cells to characterize structural and functional properties of M2BP. Both fragments were obtained in a native and glycosylated form, as analyzed by CD spectroscopy, trypsin susceptibility, and enzymatic deglycosylation. These results strongly suggest that both fragments are autonomous folding units. All three potential N-glycosylation sites in M2BP-1,2 and all four in M2BP-3,4 were found to be occupied. M2BP-1,2 expressed in tunicamycin-treated cells contained no glycosyl residues, indicating that O-glycosylation is not occurring. Ultracentrifugation revealed that M2BP-1,2 is homogeneously dimeric in the nanomolar range reflecting the properties of intact M2BP. Domain 2 (BTB/POZ domain) is thus identified as the dimerization domain of M2BP, because it has been formerly shown that recombinant domain 1 is monomeric. M2BP-3,4 showed a concentration-dependent self-association, and aggregates of different size and shape were shown by electron microscopy. In contrast to this irregular aggregation of M2BP-3,4, it has been formerly shown that a fragment comprising domains 2-4 still has the ability to form ring-like structures, although the rings are protein-filled, and thus domain 2 appears to be indispensable for ring formation. Solid phase assays showed that M2BP-3,4 contains binding sites for galectin-3, nidogen, and collagens V and VI, whereas M2BP-1,2 is inactive in binding. Both fragments showed no cell adhesive activity in contrast to native M2BP, suggesting that a concerted binding action and/or multivalent interactions of rings are necessary for cell attachment.
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PMID:Functional studies on recombinant domains of Mac-2-binding protein. 1186 35

Among the cereals, wheat, rye, barley and oats, have been reported to cause protein contact dermatitis. However, in these cases neither the involvement of an immunological mechanism nor the role of specific protein(s) has been demonstrated. We present a case of protein contact dermatitis from corn. The patient presented with a Type I sensitization to corn, as shown by the presence of specific immunoglobulin (Ig)E and positivity to prick tests with both a flour suspension and the salt-soluble protein fraction of this cereal. The same corn preparations induced a strong urticarial reaction on scratch testing. This reaction was followed several days later by the appearance of erythema and then eczema at the site of application. When boiled, these preparations became inactive on both prick and scratch testing. Patch tests were negative in all cases. Immunoblotting performed with the patient's serum showed the presence of a unique IgE-binding protein band with a molecular weight of around 14 kDa, belonging to the salt-soluble corn protein fraction. Our results give the first clear evidence that cornflour can induce protein contact dermatitis. The IgE-binding 14-kDa protein has characteristics identical to those of the trypsin/alpha-amylase inhibitors from cereals.
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PMID:Contact urticaria and protein contact dermatitis from corn in a patient with serum IgE specific for a salt-soluble corn protein of low molecular weight. 1537 49

Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: nontumorigenic MCF10A, premalignant/tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com, and tumorigenic/metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column, and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui et al. J. Proteome Res. 2006, 5, 899-906). The search files produced from five analyses (three separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D, and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g., actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of nonclassical secretion (SecretomeP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included. The protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate, and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.
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PMID:Identification of differentially secreted biomarkers using LC-MS/MS in isogenic cell lines representing a progression of breast cancer. 1760 9

We have previously demonstrated that neuroblastoma cells increase the expression of interleukin-6 by bone marrow stromal cells and that stimulation does not require cell-cell contact. In this study we report the purification and identification of a protein secreted by neuroblastoma cells that stimulates interleukin-6 production by stromal cells. Using a series of chromatographic purification steps including heparin-affinity, ion exchange, and molecular sieve chromatography followed by trypsin digestion and liquid chromatography tandem mass spectrometry, we identified in serum-free conditioned medium of neuroblastoma cells several secreted peptides including galectin-3-binding protein, also known as 90-kDa Mac-2-binding protein. We demonstrated the presence of the galectin-3-binding protein in the conditioned medium of several neuroblastoma cell lines and in chromatographic fractions with interleukin-6 stimulatory activity. Consistently, bone marrow stromal cells express galectin-3, the receptor for galectin-3-binding protein. Supporting a role for galectin-3-binding protein in stimulating interleukin-6 expression in bone marrow stromal cells, we observed that recombinant galectin-3-binding protein stimulated interleukin-6 expression in these cells and that interleukin-6 stimulation by neuroblastoma-conditioned medium was inhibited in the presence of lactose or a neutralizing anti-galectin-3 antibody. Down-regulation of galectin-3-binding protein expression in neuroblastoma cells also decreased the interleukin-6 stimulatory activity of the conditioned medium on bone marrow stromal cells. We also provide evidence that stimulation of interleukin-6 by galectin-3-binding protein involves activation of the Erk1/2 pathway. The data, thus, identifies galectin-3-binding protein as a factor secreted by neuroblastoma cells that stimulates the expression of interleukin-6 in bone marrow stromal cells and provides a novel function for this protein in cancer progression.
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PMID:Identification of galectin-3-binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma. 1845 Jul 43

A new galactose-specific lectin was purified from seeds of a Caesalpinoideae plant, Bauhinia variegata, by affinity chromatography on lactose-agarose. Protein extracts haemagglutinated rabbit and human erythrocytes (native and treated with proteolytic enzymes), showing preference for rabbit blood treated with papain and trypsin. Among various carbohydrates tested, the lectin was best inhibited by D-galactose and its derivatives, especially lactose. SDS-PAGE showed that the lectin, named BVL, has a pattern similar to other lectins isolated from the same genus, Bauhinia purpurea agglutinin (BPA). The molecular mass of BVL subunit is 32 871 Da, determined by MALDI-TOF spectrometry. DNA extracted from B.variegata young leaves and primers designed according to the B. purpurea lectin were used to generate specific fragments which were cloned and sequenced, revealing two distinct isoforms. The bvl gene sequence comprised an open reading frame of 876 base pairs which encodes a protein of 291 amino acids. The protein carried a putative signal peptide. The mature protein was predicted to have 263 amino acid residues and 28 963 Da in size.
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PMID:Purification and molecular cloning of a new galactose-specific lectin from Bauhinia variegata seeds. 1900 35

The glycophenotyping of mammalian cells with plant lectins maps aspects of the glycomic profile and disease-associated alterations. A salient step toward delineating their functional dimension is the detection of endogenous lectins. They can translate sugar-encoded changes into cellular responses. Among them, the members of the lectin family of galectins are emerging regulators of cell adhesion, migration and proliferation. Focusing on galectins-1, -3 and -7, we addressed the issue whether their expression is regulated during wound healing in porcine skin as model. A conspicuous upregulation is detected for galectin-1 in the dermis and a neoexpression in the epidermis, where an increased level of galectin-7 was also found. Applying biotinylated tissue lectins as probes, the signal intensities for accessible binding sites decreased, intimating an interaction of the cell lectin with reactive sites. In contrast, galectin-3 parameters remained rather constant. Of note, epidermal cells in culture also showed an increase in expression/presence of galectin-1, measured on the levels of mRNA and protein, in this case by Western blotting and quantitative immunocytochemistry. Used as matrix, galectin-1 conferred resistance to trypsin treatment to attached human keratinocytes and reduced migration into scratch-wound areas in vitro. This report thus presents new information on endogenous lectins in wound healing and differential regulation among the three tested cases.
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PMID:Differential regulation of galectin expression/reactivity during wound healing in porcine skin and in cultures of epidermal cells with functional impact on migration. 1909 45

Administration of the multipotent hematopoietic progenitor cell (HPC) line DKmix improved cardiac function after myocardial infarction and accelerated dermal wound healing due to paracrine mechanisms. The aim of this study was to analyse the secreted proteins of DKmix cells in order to identify the responsible paracrine factors and assess their relevance to the wide spectrum of therapeutic effects. A mass spectrometry (MS)-based approach was used to identify secreted proteins of DKmix cells. Serum free culture supernatants of DKmix-conditioned medium were collected and the proteins present were separated, digested by trypsin and the resulting peptides were then analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) MS. Overall 95 different proteins were identified. Among them, secretory proteins galectin-3 and gelsolin were identified. These proteins are known to stimulate cell migration and influence wound healing and cardiac remodelling. The remaining proteins originate from intracellular compartments like cytoplasm (69%), nucleus (12%), mitochondria (4%), and cytoplasmic membrane (3%) indicating permeable or leaky DKmix cells in the conditioned medium. Additionally, a sandwich immunoassay was used to detect and quantify cytokines and chemokines. Interleukin-6 (IL-6), interleukin-13 (IL-13), monocyte-chemoattractant protein-1 (MCP-1), monocyte-chemoattractant protein-3 (MCP-3), monocyte-chemoattractant protein-1alpha (MIP-1alpha) and monocyte-chemoattractant protein-1beta (MIP-1beta) were detected in low concentrations. This study identified a subset of proteins present in the DKmix-conditioned medium that act as paracrine modulators of tissue repair. Moreover, it suggests that DKmix-derived conditioned medium might have therapeutic potency by promoting tissue regeneration.
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PMID:Secreted proteome of the murine multipotent hematopoietic progenitor cell line DKmix. 2012 8


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