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)

A galactose-specific lectin has earlier been isolated from the seeds of Dolichos lablab in our laboratory by conventional protein purification methods. We now established conditions to bind the lectin on Sepharose-galactose gel in the presence of 1.5 M ammonium sulfate in Tris-buffered saline, pH 7.4. It can be specifically eluted with 0.3 M galactose. The purified lectin is a glycoprotein, binds to Con A, agglutinates erythrocytes, and has an apparent native molecular weight of 120 +/- 5 kDa. In SDS-PAGE under reducing conditions, it dissociates into two subunits of molecular mass (Mr) 31 and 29 kDa. Among a number of sugars tested for inhibitory activity of the lectin, galactose was found to be a potent inhibitor. Rabbit polyclonal antibody to the purified lectin specifically reacted with the lectin subunits in Western blot analysis and additionally, an antibody raised to the isolated 31 kDa subunit show reactivity with both the subunits. Amino terminal sequences of both the subunits are identical. The purified lectin is stable up to 40 degrees C with a pH optimum of 7.4. The lectin has a high content of acidic amino acids and lacks sulfur-containing amino acids. Chemical modification of the lectin with group-specific reagents indicates the possible role of histidine, lysine, and tyrosine residues in lectin activity.
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PMID:Affinity purification, physicochemical and immunological characterization of a galactose-specific lectin from the seeds of Dolichos lablab (Indian lablab beans). 1612 71

Our previous isothermal titration microcalorimetry (ITC) studies of the binding of synthetic multivalent carbohydrates to the Man/Glc-specific lectins concanavalin A (ConA) and Dioclea grandiflora lectin (DGL) showed negative binding cooperativity that was due to the carbohydrate ligands and not the proteins [Dam, T. K., et al. (2002) Biochemistry 41, 1351-1358]. The negative cooperativity was associated with the decreasing functional valence of the carbohydrates upon progressive binding of their epitopes. The present study also shows negative cooperativity in the ITC binding data of asialofetuin (ASF), a glycoprotein that possesses nine LacNAc epitopes, to galectin-1, -2, -3, -4, -5, and -7, and truncated, monomer versions of galectin-3 and -5, which are members of a family of animal lectins. Although the observed K(a) values for binding of ASF to the galectins and two truncated forms are only 50-80-fold greater than that of LacNAc, analysis of the data in terms of the relationship between the observed macroscopic free energy of binding and the decreasing microscopic free energies of binding of the epitopes shows that the first LacNAc epitope of ASF binds with approximately 6000-fold higher affinity than the last epitope. Thus, the microscopic binding constants of the galectins for the first epitope(s) of ASF are in the nanomolar range, with a gradient of decreasing binding constants of the remaining epitopes. The results indicate that the above galectins bind with fractional, high affinities to multivalent glycoproteins such as ASF, independent of the quaternary structures of the galectins. These findings have important implications for the binding of galectins to multivalent carbohydrate receptors.
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PMID:Galectins bind to the multivalent glycoprotein asialofetuin with enhanced affinities and a gradient of decreasing binding constants. 1615 68

Galectins are a family of mammalian beta-galactoside-binding proteins that positively and negatively regulate T cell death. Extracellular galectin-1 directly induces death of T cells and thymocytes, while intracellular galectin-3 blocks T cell death. In contrast to the antiapoptotic function of intracellular galectin-3, we demonstrate that extracellular galectin-3 directly induces death of human thymocytes and T cells. However, events in galectin-3- and galectin-1-induced cell death differ in a number of ways. Thymocyte subsets demonstrate different susceptibility to the two galectins: whereas galectin-1 kills double-negative and double-positive human thymocytes with equal efficiency, galectin-3 preferentially kills double-negative thymocytes. Galectin-3 binds to a complement of T cell surface glycoprotein receptors distinct from that recognized by galectin-1. Of these glycoprotein receptors, CD45 and CD71, but not CD29 and CD43, appear to be involved in galectin-3-induced T cell death. In addition, CD7 that is required for galectin-1-induced death is not required for death triggered by galectin-3. Following galectin-3 binding, CD45 remains uniformly distributed on the cell surface, in contrast to the CD45 clustering induced by galectin-1. Thus, extracellular galectin-3 and galectin-1 induce death of T cells through distinct cell surface events. However, as galectin-3 and galectin-1 cell death are neither additive nor synergistic, the two death pathways may converge inside the cell.
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PMID:Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. 1639 61

alpha2-seminoglycoprotein (alpha2-SGP), purified from human seminal plasma, is a carrier of glycoprotein for the ABO blood grouping. The alpha2-SGP exists in the secretions of the seminal vesicle and various glands. However, the function of alpha2-SGP is, as yet, unknown. In this study, we determined that two internal amino acid sequences of 8 and 12 residues of alpha2-SGP were Ala-Val-Asp-Thr-Trp-Ser-Trp-Gly and Thr-Leu-Gln-Ala-Leu-Glu-Phe-His-Thr-Val-Pro-Phe. These sequences were completely coincident with the domain 3 of human Mac-2 binding protein (M2BP), which was identified as a tumor-associated antigen. In addition, we also confirmed an alpha2-SGP binding activity to galectin-3 that was one of a ligand for M2BP, and the immunological cross-reactivity between alpha2-SGP and M2BP. These findings strongly suggested that alpha2-SGP was identical with M2BP.
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PMID:Homology between ABH-carrier alpha2-seminoglycoprotein and Mac-2 binding protein. 1690 10

Binding of galactose-specific lectin PNA to the surface of erythrocyte membrane decreased by more than 90% in stressed rats. In the presence of sodium dodecyl sulfate, the lectin-binding fraction was electrophoretically separated into 3 major glycoprotein subfractions with molecular weights of 25, 37, and 50 kDa.
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PMID:Changes on the surface of erythrocyte membrane during chronic stress in rats. 1718 Oct 58

Epithelial cells are characterized by their polarized organization based on an apical membrane that is separated from the basolateral membrane domain by tight junctions. Maintenance of this morphology is guaranteed by highly specific sorting machinery that separates lipids and proteins into different carrier populations for the apical or basolateral cell surface. Lipid-raft-independent apical carrier vesicles harbour the beta-galactoside-binding lectin galectin-3, which interacts directly with apical cargo in a glycan-dependent manner. These glycoproteins are mistargeted to the basolateral membrane in galectin-3-depleted cells, dedicating a central role to this lectin in raft-independent sorting as apical receptor. Here, we demonstrate that high-molecular-weight clusters are exclusively formed in the presence of galectin-3. Their stability is sensitive to increased carbohydrate concentrations, and cluster formation as well as apical sorting are perturbed in glycosylation-deficient Madin-Darby canine kidney (MDCK) II cells. Together, our data suggest that glycoprotein cross-linking by galectin-3 is required for apical sorting of non-raft-associated cargo.
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PMID:Apical sorting by galectin-3-dependent glycoprotein clustering. 1731 96

Cell-surface glycoprotein receptors have varying numbers of N-glycan sites. In this issue of Cell, Lau et al. (2007) report that increasing intracellular UDP-GlcNAc leads to increased branching of N-glycans, increased receptor association with cell-surface galectin-3, and enhanced signaling. They also show that the kinetics of this response differ between growth-promoting receptors, which have 8-16 N-glycans, and those that induce growth arrest, which have very few N-glycans, suggesting that hexosamine flux may regulate the transition from growth to arrest.
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PMID:A method to the madness of N-glycan complexity? 1741 91

The galectin family of lectins regulates multiple biologic functions, such as development, inflammation, immunity, and cancer. One common function of several galectins is the ability to trigger T cell death. However, differences among the death pathways triggered by various galectins with regard to glycoprotein receptors, intracellular death pathways, and target cell specificity are not well understood. Specifically, galectin-9 and galectin-1 both kill thymocytes, peripheral T cells, and T cell lines; however, we have found that galectin-9 and galectin-1 require different glycan ligands and glycoprotein receptors to trigger T cell death. The two galectins also utilize different intracellular death pathways, as galectin-9, but not galectin-1, T cell death was blocked by intracellular Bcl-2, whereas galectin-1, but not galectin-9, T cell death was blocked by intracellular galectin-3. Target cell susceptibility also differed between the two galectins, as galectin-9 and galectin-1 killed different subsets of murine thymocytes. To define structural features responsible for distinct activities of the tandem repeat galectin-9 and dimeric galectin-1, we created a series of bivalent constructs with galectin-9 and galectin-1 carbohydrate recognition domains connected by different peptide linkers. We found that the N-terminal carbohydrate recognition domain and linker peptide contributed to the potency of these constructs. However, we found that the C-terminal carbohydrate recognition domain was the primary determinant of receptor recognition, death pathway signaling, and target cell susceptibility. Thus, carbohydrate recognition domain specificity, presentation, and valency make distinct contributions to the specific effects of different galectins in initiating T cell death.
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PMID:Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. 1825 91

Growing insights into the functionality of lectin-carbohydrate interactions are identifying attractive new targets for drug design. As glycan recognition is regulated by the structure of the sugar epitope and also by topological aspects of its presentation, a suitable arrangement of ligands in synthetic glycoclusters has the potential to enhance their avidity and selectivity. If adequately realized, such compounds might find medical applications. This is why we focused on lectins of clinical interest, acting either as a potent biohazard (a toxin from Viscum album L. akin to ricin) or as a factor in tumor progression (human galectins-1, -3, and -4). Using a set of 14 calix[n]arenes (n=4, 6, and 8) with thiourea-linked galactose or lactose moieties, we first ascertained the lectin-binding properties of the derivatized sugar head groups conjugated to the synthetic macrocycles. Despite their high degree of flexibility, the calix[6,8]arenes proved especially effective for the plant AB-toxin, in the solid-phase model system with a single glycoprotein (asialofetuin) and with human tumor cells in vitro. The bioactivity of the calix[n]arenes was also proven for human galectins. Notably, selectivity for the tested tandem-repeat-type galectin-4 among the three subgroups was determined at the level of solid-phase and cell assays, the large flexible macrocycles again figuring prominently as inhibitors. Alternate and cone versions of calix[4]arene with lactose units distinguished between galectins-1 and -4 versus galectin-3 in cell assays. The results thus revealed bioactivity of galactose-/lactose-presenting calix[n]arenes for medically relevant lectins and selectivity within the family of adhesion/growth-regulatory human galectins.
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PMID:Calix[n]arene-based glycoclusters: bioactivity of thiourea-linked galactose/lactose moieties as inhibitors of binding of medically relevant lectins to a glycoprotein and cell-surface glycoconjugates and selectivity among human adhesion/growth-regulatory galectins. 1850 38

A 13-month-old Korean female presented with Cushing disease and diabetes insipidus. On MRI, a 3.5-cm, focally cystic, contrast-enhancing, sellar and suprasellar mass was noted. Aside from blood adrenocorticotropin (ACTH) and cortisol elevation, other pituitary hormone blood levels were normal or markedly reduced. The subtotally resected lesion consisted of synaptophysin-immunoreactive lobules of (a) large, polygonal, amphophilic, PAS-positive cells immunoreactive for ACTH, beta-endorphin, alpha melanocyte stimulating hormone (MSH), and keratin (CAM5.2) in some cells showing Crooke hyaline change, (b) less frequent acidophilic, growth hormone (GH) immunoreactive cells, and (c) rare luteinizing hormone (LH) and/or alpha subunit immunopositive cells. Also conspicuous were smaller cells resembling Rathke-type epithelium forming rosettes to sizable glands immunoreactive for EMA, keratin, S-100 protein, galectin-3 and rarely for synaptophysin and/or one of the above-noted adenohypophysial hormones. Transcription factors, including Neuro-D1 and Pit-1, were present in ACTH- and GH-producing cells, respectively, but only in occasional Rathke-type cells. The MIB-1 labeling index (LI) was 1.5% in secretory cells and 39% in Rathke-type epithelium. Ultrastructurally, the tissue resembled fetal pituitary of 10-12 weeks gestation and contained fully differentiated corticotrophs and somatotrophs, scant cells of glycoprotein-hormone producing type with small secretory granules, and glandular epithelial cells consistent with committed, but largely undifferentiated Rathke-type epithelium. We consider the tumor as a pituitary blastoma, a lesion composed of multiple cell types common to the development of the affected organ based upon (a) prominence of primitive Rathke-type epithelium, (b) disposition of secretory cells in lobules rather than acini, (c) the limited range of secretory cells represented, (d) the presence of their corresponding transcription factors, and (e) ultrastructural features indicating orderly development of the 10- to 12-week embryonic stage.
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PMID:Pituitary blastoma. 1855 Dec 99


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