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 nucleotide sequence of a partial cDNA for the bovine low-density lipoprotein (LDL) receptor revealed an open reading frame of 264 amino acids that encodes the COOH-terminal 25% of the receptor protein. The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids and an externally disposed stretch of 42 amino acids, that is rich in serine and threonine residues and appears to be the site of O-linked glycosylation. This orientation was confirmed by proteolysis experiments in which the relevant fragments were localized by blotting with anti-peptide antibodies and a galactose-specific lectin. The extracytoplasmic domain of the LDL receptor contains a region that is 38% identical with a 96 amino acid sequence in the precursor to mouse epidermal growth factor (EGF), a peptide hormone. This unexpected homology raises the possibility that proteins involved in growth stimulation (e.g., EGF precursor) and nutrient delivery (e.g., LDL receptor) may have a common evolutionary origin.
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PMID:Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor. 632 78

In this review, we present and discuss a selected panel of antibody-defined markers expressed during different stages of mouse macrophage development. We distinguish four categories of markers, which are characteristic of: (1) macrophage precursors and immature macrophages (ER-MP12, ER-MP20, ER-MP54, ER-MP58); (2) mature macrophages in general (F4/80, BM8, Mac-1, Mac-2, ER-BMDM1); (3) macrophage subsets (ER-HR3, ER-MP23, ER-TR9, Forssman antigen, MOMA-1, MOMA-2, Monts-4, SER-4), and (4) IFN-gamma-stimulated macrophages (H-2Ia, LFA-1, ICAM-1, 158.2, MBR-2, TM-2, TM-4, and TM-5). It should be noted that many of the markers in this last category are inducible by other stimuli as well. The rigid classification of markers into four separate groups should be regarded as a digitalization of a continuum, thus inevitably implicating a simplification of the complex phenotypic changes that occur during mononuclear phagocyte development. Nevertheless, the current selection of antibodies against markers for different developmental stages of macrophages constitutes an important tool for characterization of mouse macrophages which participate in various biological processes.
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PMID:Markers of mouse macrophage development detected by monoclonal antibodies. 808 37

Galectin-3 is a member of the beta-galactoside-binding protein family shown to be involved in tumor progression and metastasis. It has a unique primary structure consisting of three domains: a 12-amino acid leader sequence containing a casein kinase I serine phosphorylation site, which is preceded by a collagenase-sensitive Pro-Gly-rich motif, and a COOH-terminal half encompassing the carbohydrate-binding site. To study the functional role of the unusual leader sequence of galectin-3, a mutant cDNA that causes an 11-amino acid deletion in the NH2-terminal region was generated and expressed in galectin-3-null BT-549 human breast carcinoma cells. Deletion of the NH2 terminus resulted in abolition of the secretion of truncated galectin-3, loss of nuclear localization, and reduced carbohydrate-mediated functions compared with the wild-type protein. When green fluorescent protein was fused to the galectin-3 leader sequence and transiently transfected into BT-549 cells, the uniform cellular distribution of native green fluorescent protein was changed mainly to a nuclear pattern. To further investigate whether the functional changes observed in a galectin-3 with the 11 NH2-terminal amino acids deleted were due to loss of phosphorylation at Ser6, two point mutations were created at this serine: Ser6-->Ala and Ser6-->Glu. No obvious difference was observed in cellular localization between wild-type and Ser6-mutated transfectants. These results suggest a structural role for the NH2 terminus leader motif of galectin-3 in determining its cellular targeting and biological functions independent of phosphorylation.
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PMID:The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells. 1062 18

Galectin-3, a beta-galactoside-binding protein, is implicated in cell growth, adhesion, differentiation, and tumor progression by interactions with its ligands. Recent studies have revealed that galectin-3 suppresses apoptosis and anoikis that contribute to cell survival during metastatic cascades. Previously, it has been shown that human galectin-3 undergoes post-translational signaling modification of Ser(6) phosphorylation that acts as an "on/off" switch for its sugar-binding capability. We questioned whether galectin-3 phosphorylation is required for its anti-apoptotic function. Serine to alanine (S6A) and serine to glutamic acid (S6E) mutations were produced at the casein kinase I phosphorylation site in galectin-3. The cDNAs were transfected into a breast carcinoma cell line BT-549 that innately expresses no galectin-3. Metabolic labeling revealed that only wild type galectin-3 undergoes phosphorylation in vivo. Expression of Ser(6) mutants of galectin-3 failed to protect cells from cisplatin-induced cell death and poly(ADP-ribose) polymerase from degradation when compared with wild type galectin-3. The non-phosphorylated galectin-3 mutants failed to protect cells from anoikis with G(1) arrest when cells were cultured in suspension. In response to a loss of cell-substrate interactions, only cells expressing wild type galectin-3 down-regulated cyclin A expression and up-regulated cyclin D(1) and cyclin-dependent kinase inhibitors, i.e. p21(WAF1/CIP1) and p27(KIP1) expression levels. These results demonstrate that galectin-3 phosphorylation regulates its anti-apoptotic signaling activity.
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PMID:Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. 1172 77

DMBT1 and galectin-3 are potential interacting proteins with presumably complex roles in tumorigenesis. While at present a variety of mechanisms are discussed for DMBT1 and its participation in cancer, galectin-3 is commonly known to exert tumor-promoting effects. However, in vitro studies in a rodent system have suggested that DMBT1/galectin-3 interaction in the ECM triggers epithelial differentiation, which would point to tumor-suppressive properties. To improve the understanding of DMBT1/galectin-3 action in cancer, we carried out studies in skin cancer of different origins. Mutational analyses of DMBT1 identified a missense mutation in 1 of 13 melanoma cell lines. It led to an exchange of an evolutionary conserved proline residue for serine and located within the second CUB domain of DMBT1. Immunohistochemical analyses demonstrated absence of DMBT1/galectin-3 expression from melanocytes but induction of DMBT1 expression in 1 of 8 nevi and 1 of 11 melanomas and of galectin-3 expression in 3 of 8 nevi and 4 of 8 melanomas. These data suggest that DMBT1 and galectin-3 are unlikely to act as classical tumor suppressors in melanomas. DMBT1 and galectin-3 appear to be secreted to the ECM by epithelial cells within the epidermis and the hair follicle. Compared to the flanking normal epidermis, skin tumors of epithelial origin frequently displayed downregulation of DMBT1 (18 of 19 cases) and galectin-3 (12 of 12 cases). Thus, loss of DMBT1/galectin-3 expression may play a role in the genesis of epithelial skin cancer. This would support the view that galectin-3 can exert tumor-suppressive effects in certain scenarios, and DMBT1/galectin-3-mediated differentiation represents a candidate mechanism for this effect.
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PMID:Frequent downregulation of DMBT1 and galectin-3 in epithelial skin cancer. 1267 72

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.
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PMID:Mucins and mucin binding proteins in colorectal cancer. 1500 Jan 51

Galectin-3 (Gal-3), a member of the beta-galactoside binding protein family containing the NWGR antideath motif of the Bcl-2 protein family, is involved in various aspects of cancer progression. Previously, it has been shown that the antiapoptotic activity of Gal-3 is regulated by the phosphorylation at Ser(6) by casein kinase 1 (CK1). Here we questioned how phosphorylation at Ser(6) regulates Gal-3 function. We have generated serine-to-alanine (S6A) and serine-to-glutamic acid (S6E) Gal-3 mutants and transfected them into the BT-549 human breast carcinoma cell line, which does not express Gal-3. BT-549 cell clones expressing wild-type (wt) and mutant Gal-3 were exposed to chemotherapeutic anticancer drugs. In response to the apoptotic insults, phosphorylated wt Gal-3 was exported from the nucleus to the cytoplasm and protected the BT-549 cells from drug-induced apoptosis while nonphosphorylated mutant Gal-3 neither was exported from the nucleus nor protected BT-549 cells from drug-induced apoptosis. Furthermore, leptomycin B, a nuclear export inhibitor, increased the cisplatin-induced apoptosis of Gal-3 expressing BT-549 cells. These results suggest that Ser(6) phosphoryaltion acts as a molecular switch for its cellular translocation from the nucleus to the cytoplasm and, as a result, regulates the antiapoptotic activity of Gal-3.
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PMID:Nuclear export of phosphorylated galectin-3 regulates its antiapoptotic activity in response to chemotherapeutic drugs. 1512 58

Entamoeba histolytica is an intestinal ameba that causes dysentery and liver abscesses. Cytotoxicity and phagocytosis of host cells characterize invasive E. histolytica infection. Prior to phagocytosis of host cells, E. histolytica induces apoptotic host cell death, using a mechanism that requires contact via an amebic galactose-specific lectin. However, lectin inhibition only partially blocks phagocytosis of already dead cells, implicating at least one additional receptor in phagocytosis. To identify receptors for engulfment of apoptotic cells, monoclonal antibodies against E. histolytica membrane antigens were screened for inhibition of phagocytosis. Of 43 antibodies screened, one blocked lectin-independent uptake of apoptotic cells, with >90% inhibition at a dose of 20 microg/ml (P < 0.0003 versus control). The same antibody also inhibited adherence to apoptotic lymphocytes and, to a lesser extent, adherence to and killing of viable lymphocytes. The antigen recognized by the inhibitory antibody was purified by affinity chromatography and identified by liquid chromatography-mass spectrometry as the serine-rich E. histolytica protein (SREHP). Consistent with this, the inhibitory antibody bound to recombinant SREHP present in bacterial lysates on immunoblots. The SREHP is an abundant immunogenic surface protein of unclear function. The results of this unbiased antibody screen strongly implicate the SREHP as a participant in E. histolytica phagocytosis and suggest that it may play an important role in adherence to apoptotic cells.
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PMID:Participation of the serine-rich Entamoeba histolytica protein in amebic phagocytosis of apoptotic host cells. 1808 7

Mucins are major components in mucus secretions and apical cell membranes on wet-surfaced epithelia. Structurally, they are characterized by the presence of tandem repeat domains containing heavily O-glycosylated serine and threonine residues. O-glycans contribute to maintaining the highly extended and rigid structure of mucins, conferring to them specific physical and biological properties essential for their protective functions. at the ocular surface epithelia, mucin-type O-glycan chains are short and predominantly sialylated, perhaps reflecting specific requirements of the ocular surface. Traditionally, secreted mucins and their O-glycans in the tear film have been involved in the clearance of debris and pathogens from the surface of the eye. New evidence, however, shows that O-glycans on the cell-surface glycocalyx have additional biological roles in the protection of corneal and conjunctival epithelia, such as preventing bacterial adhesion, promoting boundary lubrication, and maintaining the epithelial barrier function through their interaction with galectin-3. Abnormalities in mucin-type O-glycosylation have been identified in many disorders where the stability of the ocular surface is compromised. This review summarizes recent advances in understanding the structure, biosynthesis, and function of mucin-type O-glycans at the ocular surface and their alteration in ocular surface disease.
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PMID:Structure and biological roles of mucin-type O-glycans at the ocular surface. 2010 3

Serine phosphorylation of the beta-galactoside-binding protein galectin-3 (Gal-3) impacts nuclear localization but has unknown consequences for extracellular activities. Herein, we reveal that the phosphorylated form of galectin-3 (pGal-3), adsorbed to substratum surfaces or to heparan sulphate proteoglycans, is instrumental in promoting axon branching in cultured hippocampal neurons by local actin destabilization. pGal-3 interacts with neural cell adhesion molecule L1, and enhances L1 association with Thy-1-rich membrane microdomains. Concomitantly, membrane-actin linker proteins ezrin-radixin-moesin (ERM) are recruited to the same membrane site via interaction with the intracellular domain of L1. We propose that the local regulation of the L1-ERM-actin pathway, at the level of the plasma membrane, underlies pGal-3-induced axon branching, and that galectin phosphorylation in situ could act as a molecular switch for the axon response to Gal-3.
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PMID:Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution. 2012 15


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