Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?

Rabinovich, Gabriel A.; Baum, Linda G.; Tinari, Nicola; Paganelli, Roberto; Natoli, Clara; Liu, Fu Tong; Iacobelli, Stéfano

doi:10.1016/s1471-4906(02)02232-9

Cited by 489 publications

(406 citation statements)

References 71 publications

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“…The implication of GAL1 in various biological processes, including immune-cell homeostasis, has been extensively reported (for a review, see ref. 29). GAL1 is an apoptotic factor for thymocytes and mature T cells (30); it is involved in cell-cycle regulation and in various cell-adhesion processes.…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering

Gauthier

Rossi

Roux

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

224

213

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Although preB cell-receptor (pre-BCR) formation and cell-surface expression is essential for B cell development, pre-BCR generation of signal transduction remains elusive. Here, we report that recombinant pre-BCRs and the surrogate light chain bind specifically to the bone marrow stromal cell galectin-1 (GAL1), an S-type lectin. The surrogate light chain͞GAL1 association is a direct protein-protein interaction (K a ‫؍‬ 2 ؋ 10 6 M ؊1 ), and the NH2 extra loop of -like is the major binding element. Pre-BCR binding to stromal cells depends upon GAL1 anchoring to glycosylated counter-receptors, and these complexes completely relocalize to form a synapse at the contact zone between preB and stromal cells. This immune developmental synapse is accompanied by the initiation of intracellular tyrosine kinase activity and signal transduction from the pre-BCR.

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Section: Discussionmentioning

confidence: 99%

Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering

Gauthier

Rossi

Roux

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

224

213

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“…form a sequence-specific DNA-binding complex (14) and are frequently coactivated in spontaneous AML of BXH-2 mice (15) [forced coexpression of the two genes in murine bone marrow cells rapidly induces AML (16)]; (ii) HOX A10, which induces AML in mice (17); (iii) LMO2 (RMBT2), whose overexpression, resulting from chromosome translocations, is associated with T cell ALL (18); (iv) MYC, which has a critical role in cell proliferation and is deregulated in human lymphomas and other tumors (19); (v) LGALS1 (galectin1), which cooperates with RAS in cell transformation (20) and inhibits T cell proliferation and survival (21); and (vi) PDGFR␤ (platelet-derived growth factor receptor ␤), which is a tyrosine kinase and is deregulated through chromosome translocations and gene fusions in chronic myeloproliferative diseases (22).…”

Section: Overexpressed Oncogenes: (I) Hox A9 and Meis1 Whichmentioning

confidence: 99%

Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements

Rozovskaia¹,

Ravid-Amir²,

Тиллиб³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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The ALL-1 gene is directly involved in 5-10% of acute lymphoblastic leukemias (ALLs) and acute myeloid leukemias (AMLs) by fusion to other genes or through internal rearrangements. DNA microarrays were used to determine expression profiles of ALLs and AMLs with ALL-1 rearrangements. These profiles distinguish those tumors from other ALLs and AMLs. The expression patterns of ALL-1-associated tumors, in particular ALLs, involve oncogenes, tumor suppressors, antiapoptotic genes, drug-resistance genes, etc., and correlate with the aggressive nature of the tumors. The genes whose expression differentiates between ALLs with and without ALL-1 rearrangement were further divided into several groups, enabling separation of ALL-1-associated ALLs into two subclasses. One of the groups included 43 genes that exhibited expression profiles closely linked to ALLs with ALL-1 rearrangements. Further, there were evident differences between the expression profiles of AMLs in which ALL-1 had undergone fusion to other genes and AMLs with partial duplication of ALL-1. The extensive analysis described here pinpointed genes that might have a direct role in pathogenesis.C hromosome band 11q23 is a region of recurrent rearrangements in human acute leukemias. These rearrangements, usually in the form of reciprocal chromosome translocations, affect 5-10% of children and adults with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). The most common translocations are t(4;11) and t(9;11), accounting for 40% and 27%, respectively, of all 11q23 rearrangements. There is a strong association between leukemia phenotype and particular rearrangements. Thus, t(4;11) occurs nearly exclusively in ALL, and 85% of cases with t(9;11) are AMLs (1, 2). Essentially all 11q23 abnormalities involve the ALL-1 gene (also termed MLL, HRX, or HTRX), which rearranges with Ͼ30 partner genes to produce fusion proteins composed of ALL-1 N terminus and the C terminus of the partner protein (3, 4). A second and less frequent type of ALL-1 rearrangement does not involve partner genes but rather partial duplications of ALL-1 N-terminal segments (5). ALL-1-associated leukemias show some unusual and intriguing features (reviewed in refs. 6 and 7). First, they predominate infant acute leukemias, amounting to 80% of infants with ALL and 65% of those with AML. Second, they account for the majority of therapyrelated (secondary) leukemias, developing in 5-15% of primary cancer patients treated with drugs, such as etoposide (VP16), that inhibit DNA topoisomerase II. Third, in infant leukemia and in therapy-related leukemia the disease arises after a brief latency. In fact, studies of monozygotic twins and newborns with leukemia and analysis of neonatal blood spots from children who were diagnosed with leukemia indicate that in most or all infant leukemias ALL-1 rearrangements occur in utero. The short latency suggests that ALL-1 fusion proteins induce leukemia with few, if any, additional mutations. Fourth, prognosis of patients with 11q23 abnormalities is ...

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“…Galectin-1, expressed as a homodimer of 14.5-kDa subunits, is found in a wide range of tissue types and has been shown to play a part in the regulation of cellular growth and differentiation 2 as well as the immune response. 3 Glycoproteins, such as laminin, 4 fibronectin, 5 LAMP I and II, α 7 β 1 integrin, 7 and the glycolipid have been proposed as in vivo ligands for galectin-1. Gal-β-(1,4)-GlcNAc (LacNAc II ) (1) disaccharide units are found in each of the N-, O-, and ceramide-linked glycans found in these molecules.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of galectin‐1‐oligosaccharide complexes reveal the molecular basis for ligand diversity

et al. 2003

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Galectin-1 is a member of a protein family historically characterized by its ability to bind carbohydrates containing a terminal galactosyl residue. Galectin-1 is found in a variety of mammalian tissues as a homodimer of 14.5-kDa subunits. A number of developmental and regulatory processes have been attributed to the ability of galectin-1 to bind a variety of oligosaccharides containing the Gal-β-(1,4)-GlcNAc (LacNAc II ) sequence. To probe the origin of this permissive binding, solvated molecular dynamics (MD) simulations of several representative galectin-1-ligand complexes have been performed. Simulations of structurally defined complexes have validated the computational approach and expanded upon data obtained from X-ray crystallography and surface plasmon resonance measurements. The MD results indicate that a set of anchoring interactions between the galectin-1 carbohydrate recognition domain (CRD) and the LacNAc core are maintained for a diverse set of ligands and that substituents at the nonreducing terminus of the oligosaccharide extend into the remainder of a characteristic surface groove. The anionic nature of ligands exhibiting relatively high affinities for galectin-1 implicates electrostatic interactions in ligand selectivity, which is confirmed by a generalized Born analysis of the complexes. The results suggest that the search for a single endogenous ligand or function for this lectin may be inappropriate and instead support a more general role for galectin-1, in which the lectin is able to crosslink heterogeneous oligosaccharides displayed on a variety of cell surfaces. Such binding promiscuity provides an explanation for the variety of adhesion phenomena mediated by galectin-1.

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Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?

Cited by 489 publications

References 71 publications

Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering

Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering

Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements

Molecular dynamics simulations of galectin‐1‐oligosaccharide complexes reveal the molecular basis for ligand diversity

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