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)

Mac-2, a galactose-binding lectin secretion by activated macrophages, is the major non-integrin laminin-binding protein in these cells. Mac-2 is also expressed by epithelial cells in the intestine and kidney. We wished to identify intestinal glycoproteins other than laminin that have a high affinity for Mac-2 and that could be considered as candidate ligands or partners for this lectin in intestinal epithelium. Certain lines of human colon adenocarcinoma cells produce two Mac-2-binding glycoproteins (M2BP-1 and M2BP-2) that were identified by their avid association with Mac-2 following detergent lysis and immunoprecipitation. These glycoproteins do not share a common epitope with Mac-2, and the interaction between Mac-2 and these proteins is mediated through the carbohydrate-binding domain of Mac-2 and sugar moieties on M2BP-1 and M2BP-2. M2BP-1 (98 kDa) and M2BP-2 (70 kDa) were purified by immunoaffinity chromatography and were specifically eluted with either galactose or lactose. Peptide maps revealed that M2BP-1 and M2BP-2 are structurally related. M2BP-1 is secreted and could conceivably associate with Mac-2 extracellularly. N-terminal sequence analysis of M2BP-2 suggests that these glycoproteins represent a unique subset of candidate ligands for this mammalian beta-galactoside lectin.
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PMID:Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin. 191 96

CD14 is a glycosylphosphatidyl-inositol (GPI)-linked, 55 kDa protein that binds bacterial lipopolysaccharide (LPS, endotoxin) and plays a key role in mediating cellular responses to this potent inflammatory stimulus. Binding of LPS to CD14 is facilitated by serum proteins such as LPS binding protein (LBP). To determine if there are additional plasma proteins that bind to CD14, plasma was passed over immobilized CD14 in the presence or absence of LPS, and retained proteins were eluted. This procedure isolated not only LBP but also a serum protein known as Mac-2-binding protein (Mac-2-BP), a 97 kDa species without a known function. Binding of both LBP and Mac-2-BP to CD14 required the simultaneous presence of LPS. Experiments with purified Mac-2-BP showed that this protein alone neither enabled responses of CD14-bearing cells to LPS nor blocked the ability of plasma to enable responses of CD14-bearing cells to LPS. However, Mac-2-BP did slow the neutralization of LPS mediated by plasma lipoprotein. These studies describe the first potential function for Mac-2-BP, and suggest that neutralization of LPS in plasma may be controlled by proteins in addition to LBP and CD14.
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PMID:LPS-dependent interaction of Mac-2-binding protein with immobilized CD14. 758 57

The endogenous human tumor-associated galectin-3 (hL-31) is a functional molecule which acts as a receptor for ligands containing poly-N-acetyllactosamine sequences. However, little is known about its native ligand(s). In order to identify the ligand(s), the human melanoma cell line A375 was metabolically labeled with [3H]glucosamine, and total cell extracts and serum-free conditioned medium of the labeled cells were affinity-purified on immobilized recombinant hL-31 followed by elution with lactose, the specific sugar inhibitor of the lectin. Cellular ligands for hL-31 were found to be composed of the two lysosome-associated membrane proteins, LAMP-1 and LAMP-2, while secreted ligands consisted of two glycoproteins of 98 and 70 kDa. N-terminal protein microsequencing revealed that the 98 kDa and 70 kDa species share the same N-terminal sequence. The functional relevance of these secreted ligands was demonstrated by their ability to inhibit lectin-mediated hemagglutination in a manner similar to the specific sugar inhibitor lactose. Computer-assisted sequence library searches have identified the 98 kDa human melanoma secreted ligand to be the Mac-2-binding protein (Mac-2-BP), also known as the human lung tumor L3 antigen.
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PMID:Identification of human melanoma cellular and secreted ligands for galectin-3. 802 81

We have purified and sequenced a secreted glycoprotein from both the human breast carcinoma cell line, SK-BR-3, and human breast milk. The native protein binds specifically to a human macrophage-associated lectin known as Mac-2. This Mac-2 binding protein (Mac-2-BP) has an apparent native molecular mass of several million daltons and contains subunits of 85-97 kDa that are very susceptible to proteolysis at a dibasic cleavage site. Western analysis suggests that Mac-2-BP is found in serum, semen, saliva, urine, and tears, in addition to breast milk. The gene encoding Mac-2-BP was cloned from a cDNA bank of a human monocytic cell line, using degenerate PCR primers based on the protein sequence. Recombinant Mac-2-BP was expressed in Cos cells and secreted as a high molecular weight complex. The cDNA clone encodes a mature protein of 567 amino acids, preceded by an 18-amino acid leader. The mature protein contains 16 cysteines and has seven potential N-linked glycosylation sites. The first 106 amino acids represent a domain that is highly similar to an ancient protein superfamily defined by the macrophage scavenger receptor cysteine-rich domain.
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PMID:Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. 839 Sep 86

Galectin-3 is a beta-galactoside-specific lectin implicated in diverse processes involved in cellular interactions. Recently, the Mac-2-binding protein, a heavily N-glycosylated secreted protein with a subunit Mr of 97,000, was identified as its ligand. The present study characterizes the interaction between galectin-3 and Mac-2-binding protein in whole cells and measures their relative expression levels. Incubation of A375 cells with affinity-purified Mac-2-binding protein resulted in its binding to galectin-3 on the cell surface in a specific carbohydrate-dependent manner. Mac-2-binding protein also induced homotypic cell aggregation, which was inhibited by lactose or Fab' fragments of an anti-galectin-3 antibody. Northern blotting analysis revealed differences in the transcriptional regulation of galectin-3 and Mac-2-binding protein. These results provide the first direct evidence for a Mac-2-binding protein function and suggest that it may play a role in tumor cell embolization during metastasis through interaction with galectin-3.
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PMID:Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion. 881 52

Human 90K, also known as Mac-2 binding protein (Mac-2 BP), is a secreted glycoprotein which is widely expressed, binds to the human macrophage-associated lectin Mac-2, and may have a role in host defence. We have measured the concentrations of 90K in human breast milk from eight healthy mothers delivering mature healthy infants after full-term pregnancy using a specific immunoenzymatic assay. Maximal 90K concentrations were observed on days 2-3 post-partum, and ranged from 13.4 to 79.2 microg/ml. The concentrations of 90K in the milk had no correlation with those in the maternal blood.
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PMID:90K (Mac-2 BP) in human milk. 909 42

Human Mac-2 binding protein (M2BP) was prepared in recombinant form from the culture medium of 293 kidney cells and consisted of a 92 kDa subunit. The protein was obtained in a native state as indicated by CD spectroscopy, demonstrating alpha-helical and beta-type structure, and by protease resistance and immunological analysis. It was highly modified by N- and O-glycosylation but not by glycosaminoglycans. Ultracentrifugation showed non-covalent association into oligomers with molar masses of 1000-1500 kDa. Electron microscopy showed ring-like shapes with diameters of 30-40 nm. M2BP bound in solid-phase assays to collagens IV, V and VI, fibronectin and nidogen, but not to fibrillar collagens I and III or other basement membrane proteins. The protein also mediated adhesion of cell lines at comparable strength with laminin. Adhesion to M2BP was inhibited by antibodies to integrin beta1 subunits but not to alpha2 and alpha6 subunits, RGD peptide or lactose. This distinguishes cell adhesion of M2BP from that of laminin and excludes involvement of lactose-binding galectin-3. Immunological assays demonstrated variable secretion by cultured human cells of M2BP, which was detected in the extracellular matrix of several mouse tissues.
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PMID:Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens and fibronectin. 950 Oct 82

The multidomain Mac-2 binding protein (M2BP) is present in serum and in the extracellular matrix in the form of linear and ring-shaped oligomers, which interact with galectin-3, fibronectin, collagens, integrins and other large glycoproteins. Domain 1 of M2BP (M2BP-1) shows homology with the cysteine-rich SRCR domain of scavanger receptor. Domains 2 and 3 are related to the dimerization domains BTB/POZ and IVR of the Drosophila kelch protein. Recombinant M2BP, its N-terminal domain M2BP-1 and a fragment consisting of putative domains 2, 3 and 4 (M2BP-2,3,4) were investigated by scanning transmission electron microscopy, transmission electron microscopy, analytical ultracentrifugation and binding assays. The ring oligomers formed by the intact protein are comprised of approximately 14 nm long segments composed of two 92 kDa M2BP monomers. Although the rings vary in size, decamers predominate. The various linear oligomers also observed are probably ring precursors, dimers predominate. M2BP-1 exhibits a native fold, does not oligomerize and is inactive in cell attachment. M2BP-2,3,4 aggregates to heterogeneous, protein filled ring-like structures as shown by metal shadowed preparations. These aggregates retain the cell-adhesive potential indicating native folding. It is hypothesized that the rings provide an interaction pattern for multivalent interactions of M2BP with target molecules or complexes of ligands.
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PMID:Domain organization of Mac-2 binding protein and its oligomerization to linear and ring-like structures. 1045 90

Human Mac-2-binding protein (Mac-2-BP) is a secreted glycoprotein that is widely expressed. It binds to the human macrophage-associated lectin Mac-2 and has been suggested to have a role in host defence. Mouse cyclophilin C-associated protein (mCyCAP) is also a secreted glycoprotein that binds with high affinity to cyclophilin C in the absence of the immunosuppressive drug cyclosporin A. The two proteins share a similar domain structure and considerable sequence identity, including a highly conserved scavenger receptor cysteine-rich domain, and both of them exert their function within the immune system. To elucidate whether these molecules are also functional homologues, we compared their ligand binding properties using cell lines which express Mac-2-BP or mCyCAP as well as transfected cell lines stably expressing mCyCAP or a mutant version lacking the scavenger domain. These experiments show that Mac-2-BP is unable to bind to either human or mouse cyclophilin C and thatmCyCAP cannot bind to Mac-2. The scavenger domain is not required for the interaction between mCyCAP and cyclophilin C. We conclude that these proteins may be part of a larger family of proteins of immunological importance in which closer functional homologues might exists.
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PMID:Distinct ligand binding properties of Mac-2-binding protein and mouse cyclophilin [correction of mousephilin] C-associated protein. 1159 84

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


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