Galectin-3 Precipitates as a Pentamer with Synthetic Multivalent Carbohydrates and Forms Heterogeneous Cross-linked Complexes

Galectin-3 is unique among the galectin family of animal lectins in its biological activities and structure. Most members of the galectin family including galectin-1 possess apoptotic activities, whereas galectin-3 possesses anti-apoptotic activity. Galectin-3 is also the only chimera type galectin and consists of a nonlectin N-terminal domain and a C-terminal carbohydrate-binding domain. Recent sedimentation equilibrium and velocity studies show that murine galectin-3 is a monomer in the absence and presence of LacNAc, a monovalent sugar. However, quantitative precipitation studies in the present report indicate that galectin-3 precipitates as a pentamer with a series of divalent pentasaccharides with terminal LacNAc residues. Furthermore, the kinetics of precipitation are fast, on the order of seconds. This indicates that although the majority of galectin-3 in solution is a monomer, a rapid equilibrium exists between the monomer and a small percentage of pentamer. The latter, in turn, precipitates with the divalent oligosaccharides, resulting in rapid conversion of monomer to pentamer by mass action equilibria. Mixed quantitative precipitation experiments and electron microscopy suggest that galectin-3 forms heterogenous, disorganized cross-linking complexes with the multivalent carbohydrates. This contrasts with galectin-1 and many plant lectins that form homogeneous, organized cross-linked complexes. The results are discussed in terms of the biological properties of galectin-3. Galectin-3 is unique among the galectin family of animal lectins in its biological activities and structure. Most members of the galectin family including galectin-1 possess apoptotic activities, whereas galectin-3 possesses anti-apoptotic activity. Galectin-3 is also the only chimera type galectin and consists of a nonlectin N-terminal domain and a C-terminal carbohydrate-binding domain. Recent sedimentation equilibrium and velocity studies show that murine galectin-3 is a monomer in the absence and presence of LacNAc, a monovalent sugar. However, quantitative precipitation studies in the present report indicate that galectin-3 precipitates as a pentamer with a series of divalent pentasaccharides with terminal LacNAc residues. Furthermore, the kinetics of precipitation are fast, on the order of seconds. This indicates that although the majority of galectin-3 in solution is a monomer, a rapid equilibrium exists between the monomer and a small percentage of pentamer. The latter, in turn, precipitates with the divalent oligosaccharides, resulting in rapid conversion of monomer to pentamer by mass action equilibria. Mixed quantitative precipitation experiments and electron microscopy suggest that galectin-3 forms heterogenous, disorganized cross-linking complexes with the multivalent carbohydrates. This contrasts with galectin-1 and many plant lectins that form homogeneous, organized cross-linked complexes. The results are discussed in terms of the biological properties of galectin-3. Galectin-3 is a widely studied member of the galectin family of β-galactoside-specific animal lectins (1Liu F.-T. Clin. Immunol. 2000; 97: 79-88Crossref PubMed Scopus (192) Google Scholar, 2Barondes S.H. Cooper D.N.W. Gitt M.A. Leffler H. J. Biol. Chem. 1994; 269: 20807-20810Abstract Full Text PDF PubMed Google Scholar, 3Kasai K.-I. Hirabayashi J. J. Biochem. (Tokyo). 1996; 119: 1-8Crossref PubMed Scopus (460) Google Scholar). It is the only chimera type galectin and possesses a nonlectin N-terminal domain linked to a C-terminal carbohydrate recognition domain (CRD) 1The abbreviations used are: CRD, carbohydrate recognition domain; LacNAc, N-acetyllactosamine; ASF, asialofetuin. (2Barondes S.H. Cooper D.N.W. Gitt M.A. Leffler H. J. Biol. Chem. 1994; 269: 20807-20810Abstract Full Text PDF PubMed Google Scholar, 4Gabius H.-J. Eur. J. Biochem. 1997; 243: 543-576Crossref PubMed Scopus (492) Google Scholar). The amino acid sequence of galectin-3 varies from 243 to 286 amino acids depending on the number of tandem repeats of a peptide sequence rich in proline, glycine, and tyrosine residues in the N-terminal domain, which is species-dependent (5Cooper D.N.W. Biochim. Biophys. Acta. 2002; 1572: 209-231Crossref PubMed Scopus (530) Google Scholar). In the mammalian protein, there is also a conserved 18-amino acid N-terminal peptide sequence preceding the proline/glycine/tyrosine-rich repetitive domain that appears to have its own functions (5Cooper D.N.W. Biochim. Biophys. Acta. 2002; 1572: 209-231Crossref PubMed Scopus (530) Google Scholar). The C-terminal CRD domain of galectin-3 is homologous to that of galectin-1 and other members of the galectin family (5Cooper D.N.W. Biochim. Biophys. Acta. 2002; 1572: 209-231Crossref PubMed Scopus (530) Google Scholar, 6Jia S. Wang J.L. J. Biol. Chem. 1988; 263: 6009-6011Abstract Full Text PDF PubMed Google Scholar). Although the x-ray crystal structure of intact galectin-3 has not been determined, the x-ray crystal structure of the C-terminal CRD domain of galectin-3 has been solved (7Seetharaman J. Kanigsberg A. Slaaby R. Leffler H. Barondes S.H. Rini J.M. J. Biol. Chem. 1998; 273: 13047-13052Abstract Full Text Full Text PDF PubMed Scopus (382) Google Scholar) and shown to be a monomer and not a dimer as observed for the x-ray crystal structures of galectins-1 (8Bourne Y. Bolgiano B. Liao D.-l. Strecker G. Cantau P. Herzberg O. Feizi T. Cambillau C. Nat. Struct. Biol. 1994; 1: 863-870Crossref PubMed Scopus (224) Google Scholar), -2 (9Lobsanov Y.D. Rini J.M. Trends Glycosci. Glycotech. 1997; 9: 145-154Crossref Scopus (35) Google Scholar), and -7 (10Leonidas D. Vatzaki E.H. Vorum H. Celis J.E. Madsen P. Acharya K.R. Biochemistry. 1998; 37: 12930-13940Crossref Scopus (169) Google Scholar). Galectin-3 appears to possess many biological activities. It has been implicated in the regulation of the cell growth (11Laing J.G. Wang J.L. Biochemistry. 1988; 27: 5329-5334Crossref PubMed Scopus (99) Google Scholar, 12Moutsatsos I.K. Wade M. Schindler M. Wang J.L. Proc. Natl. Acad. Sci. U. S. A. 1987; 84: 6452-6456Crossref PubMed Scopus (245) Google Scholar), leukocyte activation (13Frigeri L.G. Zuberi R.I. Liu F.-T. Biochemistry. 1993; 32: 7644-7649Crossref PubMed Scopus (171) Google Scholar, 14Zuberi R.I. Frigeri L.G. Liu F.-T. Cell. Immunol. 1994; : 1-12Crossref PubMed Scopus (64) Google Scholar, 15Yamaoka A. Kuwabara I. Frigeri L.G. Liu F.-T. J. Immunol. 1995; 154: 3479-3487PubMed Google Scholar, 16Demetriou M. Granovsky M. Quaggin S. Dennis J.W. Nature. 2001; 409: 733-739Crossref PubMed Scopus (756) Google Scholar), induction of endothelial cell morphogenesis and angiogenesis (17Nangia-Makker P. Honjo Y. Sarvis R. Akahani S. Hogan V. Pienta K.J. Raz A. Am. J. Pathol. 2000; 156: 899-909Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar), cell adhesion (18Kuwabara I. Liu F.-T. J. Immunol. 1996; 156: 3939-3944PubMed Google Scholar, 19Bao Q. Hughes R.C. J. Cell Sci. 1995; 108: 2791-2800Crossref PubMed Google Scholar), and pre-mRNA splicing (20Dagher S.F. Wang J.L. Patterson R.J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 1213-1217Crossref PubMed Scopus (365) Google Scholar). Galectin-3 is also reported to be involved in colon cancer metastasis (21Bresalier R.S. Mazurek N. Sternberg L.R. Byrd J.C. Yunker C.K. Nangia-Makker P. Raz A. Gastroenteroloy. 1998; 115: 287-296Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar) and brain tumor progression (22Camby I. Belot N. Rorive S. Lefranc F. Maurage C.-A. Lahm H. Kaltner H. Hadari Y. Ruchoux M.-M. Brotchi J. Zick Y. Salmon I. Gabius H.-J. Kiss R. Brain Pathol. 2001; 11: 12-26Crossref PubMed Scopus (162) Google Scholar). Galectin-3 shows significant homology with the Bcl-2 class of proteins, and like Bcl-2, galectin-3 possesses anti-apoptotic activity in a variety of cells (23Yang R.-Y. Hsu D.K. Liu F.-T. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6737-6742Crossref PubMed Scopus (695) Google Scholar) in contrast to the apoptotic activities of many other members of the galectin family including galectin-1 (24Rabinovich G. Rubinstein N. Toscano M.A. Biochim. Biophys. Acta. 2002; 1572: 274-284Crossref PubMed Scopus (210) Google Scholar). Because many of the biological properties of galectin-3 depend on its carbohydrate recognition properties (5Cooper D.N.W. Biochim. Biophys. Acta. 2002; 1572: 209-231Crossref PubMed Scopus (530) Google Scholar), it is important to understand its mechanism(s) of binding to cellular carbohydrates. The x-ray crystal structure of the CRD of galectin-3 has been reported (7Seetharaman J. Kanigsberg A. Slaaby R. Leffler H. Barondes S.H. Rini J.M. J. Biol. Chem. 1998; 273: 13047-13052Abstract Full Text Full Text PDF PubMed Scopus (382) Google Scholar) but not the structure of the intact molecule. The CRD alone binds lactose but lacks the hemagglutination activity and cooperative binding associated with intact galectin-3 (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar). This suggest that the N-terminal domain is important for aggregation of the protein. Indeed purified N-terminal fragments have been found to self-associate (26Mehul B. Bawumia S. Martin S.R. Hughes R.C. J. Biol. Chem. 1994; 269: 18250-18258Abstract Full Text PDF PubMed Google Scholar). Evidence that galectin-3 self-associates in the absence of saccharides was reported using chemical cross-linking experiments (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar, 27Yang R.-Y. Hill P.N. Hsu D.K. Liu F.-T. Biochemistry. 1998; 37: 4086-4092Crossref PubMed Google Scholar) and gel electrophoresis (28Ochieng J. Platt D. Tait L. Hogan V. Raz T. Carmi P. Raz A. Biochemistry. 1993; 32: 4455-4460Crossref PubMed Scopus (96) Google Scholar). The structures appeared to be dimers when examined by electron microscopy (28Ochieng J. Platt D. Tait L. Hogan V. Raz T. Carmi P. Raz A. Biochemistry. 1993; 32: 4455-4460Crossref PubMed Scopus (96) Google Scholar). In addition, the hemagglutination activity (29Frigeri L.G. Robertson M.W. Liu F.-T. J. Biol. Chem. 1990; 265: 20763-20769Abstract Full Text PDF PubMed Google Scholar) and cooperative binding of galectin-3 to immobilized IgE (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar) and laminin (30Massa S.M. Cooper D.N.W. Leffler H. Barondes S.H. Biochemistry. 1993; 32: 260-267Crossref PubMed Scopus (239) Google Scholar) also suggest that the lectin exists as an oligomer in the presence of a multivalent glycoconjugate. However, gel filtration studies failed to detect an oligomeric form of the lectin (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar, 30Massa S.M. Cooper D.N.W. Leffler H. Barondes S.H. Biochemistry. 1993; 32: 260-267Crossref PubMed Scopus (239) Google Scholar). More recently, the quaternary structure of recombinant murine galectin-3 in solution was directly determined by sedimentation velocity and equilibrium measurements, and the results show that the lectin is predominantly a monomer (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar). Hence, to date there is no clear understanding of the relationship between the quaternary structure of galectin-3 and its multivalent carbohydrate binding properties. In the present study, quantitative precipitation, electron microscopy, and kinetic data have been obtained for binding and precipitation of murine recombinant galectin-3 with a series of divalent carbohydrates possessing terminal LacNAc residues. precipitation studies indicate that the lectin precipitates as a pentamer in the presence of the divalent carbohydrates in and that the kinetics of precipitation are that a small of oligomer is in rapid equilibrium with the monomer in solution and that mass action the monomer to which precipitates with the carbohydrates. Mixed quantitative precipitation experiments indicate that galectin-3 forms cross-linked complexes with the and electron microscopy that complexes are important the properties of galectin-3. and lactose obtained from was from by and purified as D. Brewer Biochemistry. 1994; PubMed Scopus Google Scholar). was by a I. S. P. PubMed Scopus Google Scholar). of the pentasaccharides in have been reported S. S. P. S. J.C. J. Am. Chem. 1992; Scopus Google Scholar). The structures and of carbohydrates by other of with for murine galectin-3 was a from L. Wang and the was as in the N. Q. Wang Wang J.L. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar). The a by Galectin-3 found to have by using LacNAc as a of galectin-3 was to on an an of was by galectin-3 determined using the of for galectin-3 N. Gabius H.-J. Kaltner H. Andre S. I. Liu F.-T. S. T. Brewer J. Chem. 2002; Scopus Google Scholar). mass of galectin-3 was determined by and mass and was found to be pentasaccharides used in the present directly in The carbohydrate was determined by the acid M. F. Chem. Scopus Google Scholar, Brewer 1994; PubMed Scopus Google Scholar). precipitation studies of galectin-3 with the carbohydrates in and The of the precipitation was The precipitation was to for and the was by The on and the was The obtained was with and in The of the in the was by the The of precipitation of galectin-3 with the multivalent carbohydrates was determined using a solution of the in a was with a solution of a in the and the was electron microscopy was by the of the on that been for The to on a of and The observed in a electron of Galectin-3 with and shows the rapid of galectin-3 with ASF, a of mass J. Biol. Chem. Full Text PDF PubMed Google Scholar) carbohydrate with terminal LacNAc residues G. S. H. J. Biol. Chem. 1988; 263: Full Text PDF PubMed Google Scholar) and with terminal residues B. S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The presence of LacNAc the of was also observed galectin-3 results that galectin-3 and precipitates with results obtained with although the of precipitation was that for from in a of and on the terminal LacNAc residues G. S. H. J. Biol. Chem. 1988; 263: Full Text PDF PubMed Google Scholar). The kinetics of precipitation of by galectin-3 be to of to a of galectin-3 with the shown in The of precipitation of galectin-3 with of is shown in shows the of galectin-3 in the presence of the pentasaccharides The precipitation of the with precipitation of galectin-3 with the and are shown in of the including that for the a The of was on and galectin-3 The percentage of was obtained with the galectin-3 the also the of from to a galectin-3 of in the presence of the the of precipitation, the of galectin-3 with the pentasaccharides from to of galectin-3 with of galectin-3 to the in a The precipitation of galectin-3 with of pentasaccharides not from obtained with pentasaccharides The in The not by the of the galectin-3 from to of the Galectin-3 shows the results of electron microscopy of the precipitates of galectin-3 with and structures observed in the The present shows that murine recombinant galectin-3 precipitates with a series of divalent carbohydrates possessing terminal LacNAc residues as as and results with N. Wang J.L. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar), also observed that galectin-3 precipitates with and indicate that the lectin possesses multivalent carbohydrate binding and cross-linking activity. However, to understand the of binding and cross-linking of it is to understand the relationship between the quaternary structure of the lectin and its precipitation activity. directly the structure of murine recombinant galectin-3 in sedimentation velocity and equilibrium of the (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar). show that galectin-3 is predominantly a monomer in solution the of However, a small in with the in in the sedimentation velocity experiments as a of galectin-3 that the to a small with The and of the CRD domain of galectin-3 not with of protein, with the that the N-terminal domain is for the of galectin-3 in solution (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar, B. Bawumia S. Martin S.R. Hughes R.C. J. Biol. Chem. 1994; 269: 18250-18258Abstract Full Text PDF PubMed Google Scholar) and not the C-terminal domain S. R. J. 1998; PubMed Scopus Google Scholar). sedimentation of galectin-3 in the presence of LacNAc (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar), the terminal in the pentasaccharides in and experiments the that binding of LacNAc of galectin-3. However, LacNAc not the mass the of intact galectin-3 its CRD domain (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar). galectin-3 not the binding of the LacNAc of present results show that galectin-3 precipitates with a as as that an oligomeric form of galectin-3 in to the form of the protein. also shows that galectin-3 precipitates with the pentasaccharides in This indicates the of the oligomeric form of galectin-3 be lectins not with carbohydrates Brewer PubMed Scopus Google Scholar). precipitation experiments with the pentasaccharides in the oligomeric form of the that precipitates with carbohydrates. shows the quantitative precipitation of galectin-3 in the presence of the and results observed for the The of galectin-3 show in a galectin-3 with the The of the galectin-3 monomer to the of precipitation in the from to The percentage of galectin-3 is between and with the pentasaccharides Because the of is and pentasaccharides of are to form a cross-linked Brewer PubMed Scopus Google Scholar), that galectin-3 precipitates as a pentamer with the The is shown in which also indicates that of the galectin-3 pentamer is not involved in cross-linking The of not other of the to complexes but is the of carbohydrate to for precipitation of a cross-linked of of Galectin-3 with and of a for the kinetics of precipitation of galectin-3 with ASF, and the are fast, on the order of seconds. Because the of galectin-3 appears to be a the of monomer to pentamer be to precipitation of the pentamer to be Hence, the galectin-3 pentamer is by monomer by mass action as shown in by mass action and not a in the to is by the that galectin-3 a monomer in the presence of LacNAc (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar), the binding on the pentasaccharides in and precipitation of the cross-linked complexes of galectin-3 and from solution to of the lectin the mass action conversion of monomer to also binding of the galectin-3 oligomer to multivalent cell carbohydrate on the of also that there be an equilibrium between of galectin-3 have the N-terminal domain which is with the sedimentation data for galectin-3 (31Morris S. Ahmad N. Andre S. Kaltner H. Gabius H.-J. Brenowitz M. Brewer F. Glycobiology. 2004; (in press)PubMed Google Scholar). of galectin-3 with its the N-terminal domain and directly involved in an equilibrium with the oligomeric form of the protein. The in is with the that the N-terminal domain of galectin-3 is for the of the (25Hsu D.K. Zuberi R.I. Liu F.-T. J. Biol. Chem. 1992; 267: 14167-14174Abstract Full Text PDF PubMed Google Scholar, B. Bawumia S. Martin S.R. Hughes R.C. J. Biol. Chem. 1994; 269: 18250-18258Abstract Full Text PDF PubMed Google Scholar). the N-terminal of the oligomer of galectin-3 are to be the oligomer also the of binding of galectin-3 (30Massa S.M. Cooper D.N.W. Leffler H. Barondes S.H. Biochemistry. 1993; 32: 260-267Crossref PubMed Scopus (239) Google Scholar). The of galectin-3 to galectin-3 is reported to binding of the lectin to immobilized a The of galectin-3 the of oligomeric galectin-3 in solution by the shown in This in an in the of galectin-3 which in to Hence, the of galectin-3 in the binding of the lectin to the in Mixed and Evidence for the of by is galectin-3 forms cross-linked complexes with the pentasaccharides in Mixed quantitative precipitation experiments have been used to lectins form cross-linked with multivalent carbohydrates possessing D. Brewer 1994; 1: Scholar). The presence of in the precipitation of a lectin with multivalent carbohydrates is for the of cross-linked complexes of the lectin with carbohydrate Brewer PubMed Scopus Google Scholar). Mixed quantitative precipitation of galectin-3 with of the pentasaccharides in Galectin-3 was with of the and the and and the and The resulting precipitation are shown in shows a to that observed for the pentasaccharides The of galectin-3 monomer to the of precipitation is also to that observed for the pentasaccharides The percentage of galectin-3 the of precipitation in is also to the observed for The presence of a in the quantitative precipitation of galectin-3 with of the pentasaccharides that galectin-3 not form cross-linked with the of the precipitation data for the of pentasaccharides with that of the carbohydrates that galectin-3 forms cross-linked complexes with This is shown in in which a galectin-3 pentamer is involved in binding and cross-linking with electron microscopy experiments of the precipitates of galectin-3 with pentasaccharides of the pentasaccharides also to structures associated with the precipitates are results are in contrast to the electron microscopy observed for the precipitates of the with the pentasaccharides in D. L. J. F. S. Brewer Biochemistry. 1994; PubMed Scopus Google Scholar) as as of with L. J. H. Brewer Biochemistry. 1990; PubMed Scopus Google Scholar). The present electron microscopy results in are with galectin-3 cross-linked complexes as to cross-linked complexes is unique in its anti-apoptotic activity as with other including that possess apoptotic activities F.-T. Patterson R.J. Wang J.L. Biochim. Biophys. Acta. 2002; 1572: PubMed Scopus Google Scholar). In addition, galectin-3 the biological of galectin-1 the of binding in cell the binding of galectin-1 to cells to C. L.G. J. Immunol. PubMed Google Scholar) and the growth of galectin-1 binding to a cell J. C. Andre S. Kaltner H. J. V. M. Gabius H.-J. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). 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Biol. 1994; 1: 863-870Crossref PubMed Scopus (224) Google Scholar). on the other is predominantly a monomer in solution but to a pentamer by mass action in the presence of a multivalent carbohydrate Hence, galectin-3 is to a oligomer galectin-1 in the presence of multivalent carbohydrates. the type of cross-linked complexes by galectin-1 and with multivalent carbohydrates are form type cross-linked complexes Biochim. Biophys. Acta. 2002; 1572: PubMed Scopus (162) Google Scholar) with carbohydrates (8Bourne Y. Bolgiano B. Liao D.-l. Strecker G. Cantau P. Herzberg O. Feizi T. Cambillau C. Nat. Struct. Biol. 1994; 1: 863-870Crossref PubMed Scopus (224) Google Scholar) that possess a of (8Bourne Y. Bolgiano B. Liao D.-l. Strecker G. Cantau P. Herzberg O. Feizi T. Cambillau C. Nat. Struct. Biol. 1994; 1: 863-870Crossref PubMed Scopus (224) Google Scholar). also form type and cross-linked complexes with multivalent carbohydrates that possess Biochim. Biophys. Acta. 2002; 1572: PubMed Scopus (162) Google Scholar). cross-linked are organized and unique for the other the present indicates that galectin-3 forms type cross-linked complexes with multivalent carbohydrates complexes are disorganized in contrast to type cross-linked complexes. in the quaternary structures and cross-linking activities for of the of galectin-3 on the activities of galectin-1 in cell The that galectin-3 the apoptotic of galectin-1 in cells C. L.G. J. Immunol. PubMed Google be in terms of the of the galectin-3 pentamer as with the galectin-1 dimer for on the This is the carbohydrate of the LacNAc residues the of are the N. Gabius H.-J. Kaltner H. Andre S. I. Liu F.-T. S. T. Brewer J. Chem. 2002; Scopus Google Scholar). Hence, galectin-3 be to galectin-1 from the In addition, galectin-1 binding results in the of galectin-1 on the of the cells cross-linked complexes C. L.G. J. Immunol. PubMed Google Scholar). a complexes are cross-linked complexes with galectin-1 from of complexes with the The and which are associated with and activities, C. L.G. J. Immunol. PubMed Google Scholar), to be for the apoptotic of galectin-1 M. L.G. J. Immunol. 2000; PubMed Scopus Google Scholar). The of galectin-3 to the cells is to with the and of galectin-3 of This the apoptotic associated with galectin-1 Hence, galectin-3 the apoptotic activity of galectin-1 in by galectin-1 from the cells and and aggregation of the galectin-1 complexes. The mechanism(s) of galectin-3 binding to cell also to its on the growth activity of galectin-1 in a cell J. C. Andre S. Kaltner H. J. V. M. Gabius H.-J. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). The that galectin-3 the N-terminal domain to to the cells and galectin-1 activity the of galectin-3 for its activity in The is for the anti-apoptotic of galectin-3 binding to the of It is also that galectin-3 anti-apoptotic activity by mechanism(s) F.-T. Patterson R.J. Wang J.L. Biochim. Biophys. Acta. 2002; 1572: PubMed Scopus Google Scholar). by its carbohydrate recognition properties by is However, it is that galectin-3 and Bcl-2 (23Yang R.-Y. Hsu D.K. Liu F.-T. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6737-6742Crossref PubMed Scopus (695) Google Scholar). The Bcl-2 family of is also to possess anti-apoptotic activity and appears to the by J. Liu J. Wang 1997; PubMed Scopus Google Scholar). Galectin-3 the in its CRD domain (23Yang R.-Y. Hsu D.K. Liu F.-T. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6737-6742Crossref PubMed Scopus (695) Google Scholar) that is conserved among members of the Bcl-2 family and is for activity. Hence, galectin-3 appears to as as activities and by It is to the of conserved homology of galectin-3 with Bcl-2 that the also be to form cross-linked complexes with its like galectin-3. K.R. M. L.G. J. Immunol. Google Scholar) and galectin-3 M. Granovsky M. Quaggin S. Dennis J.W. Nature. 2001; 409: 733-739Crossref PubMed Scopus (756) Google Scholar) have also been shown to be involved in activation and the of The present for the and of by galectin-1 and also to the of lectins on results of the present a for the carbohydrate binding and cross-linking properties of galectin-3. The unique structure of galectin-3 to its to to that form type cross-linked complexes with multivalent carbohydrates and This contrasts with galectin-1 other members of the galectin family with divalent which form type cross-linked complexes with multivalent carbohydrates The biological of cross-linking activities, with quaternary in of the anti-apoptotic activities of galectin-3 and apoptotic activities of The of be a among the and in biological

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