Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Received on November 25, 2003; revised on June 28, 2004; accepted on June 28, 2004
Editor's note: Dr. Nathan Sharon is among an elite vanguard of scientists who pioneered the study of lectin structure and function. Since his early work on soybean agglutinin in the 1960 s, Dr. Sharon has published hundreds of papers covering all aspects of lectin recognition, from the structural basis for lectincarbohydrate interactions to clinical applications. Along with his longtime collaborator at the Weizmann Institute, Dr. Halina Lis, Dr. Sharon has not only contributed greatly to our understanding of lectins but has been a tireless and highly effective advocate for glycobiology worldwide. It is with great pleasure and appreciation that the editors provide the following historical perspective of these two leaders in the field.
![]() |
Abstract |
---|
Key words: carbohydrates / functions / glycobiology / microorganisms / plants
![]() |
Introduction |
---|
The general public became aware of ricin in 1978, following its use as a weapon in the notorious politically motivated "umbrella murder" of Georgi Markov, Bulgarian opposition writer and broadcaster in exile. Attempts to employ ricin as a potential weapon of war have been carried out by the United States during World War I; during World War II a ricin bomb was developed and tested by the British military, but it has never been deployed as a weapon for mass destruction. More recently, ricin has found its way into the arsenals of extremist individuals, groups, and governments.
![]() |
Sugar binding and blood type specificity |
---|
Already the early results obtained by Stillmark indicated some selectivity in the ricin-induced agglutination of red cells from different animals. This observation was corroborated and further extended by Karl Landsteiner from the University of Vienna, the discoverer of the human A, B, and O blood groups in 1900. Nearly a decade later he reported that the relative hemagglutinating activities of various seed extracts were quite different when tested with red blood cells from different animals (Landsteiner and Raubitschek, 1907). Because of this specificity, Landsteiner concluded that the actions of plant hemagglutinins "resemble antibody reactions in all essentials." He therefore used these proteins to illustrate the specificity concept in the introductory chapter of his classic book The Specificity of Serological Reactions (1936).
The 1940s saw the discovery, made independently by William C. Boyd at Boston University and by Karl O. Renkonen at the University of Helsinki, Finland, of the human blood group (or blood type) specificity of the hemagglutinins. They found that crude extracts of the lima bean, Phaseolus limensis, and the tufted vetch, Vicia cracca, agglutinated blood type A erythrocytes but not blood type B or O cells, whereas an extract of the asparagus pea, Lotus tetragonolobus, agglutinated specifically blood type O erythrocytes. Olavi Mäkelä (1957), a doctoral student of Renkonen, examined in 195456 extracts from seeds representing 743 plant species and 165 genera, all of the family Leguminosae, and detected hemagglutinating activity in more than one-third of them; close to one-tenth of the hemagglutinins exhibited blood type specificity. Although several of the latter were specific either for blood type O or type A, or both type A and B erythrocytes, and one, from Dolichos biflorus, reacted much better with A1 erythrocytes than with A2, only the extract from Griffonia simplicifolia (previously known as Bandeiraea simplicifolia) exhibited almost exclusively type B specificity. Since then, additional hemagglutinins specific for blood types A and O (but not B) have been discovered, as well as several for other blood types, such as N (Vicia graminea lectin), T (peanut agglutinin, PNA) and Tn (the lectins of Vicia villosa and Moluccella laevis).
The blood typespecific hemagglutinins played a crucial role in early investigations on the structural basis of the specificity of the antigens associated with the ABO blood group system. In the 1950s, Walter J. T. Morgan and Winifred M. Watkins at the Lister Institute, London, found that the agglutination of type A red cells by lima bean lectin was best inhibited by -linked N-acetyl-D-galactosamine and that of type O cells by the lectin of L. tetragonolobus was best inhibited by
-linked L-fucose. They concluded that
-N-acetyl-D-galactosamine and
-L-fucose are the sugar determinants conferring A and H(O) blood group specificity, respectively. Both conclusions have been substantiated by subsequent investigations (for a recent review, see Morgan and Watkins, 2000
). The pioneering work of Watkins and Morgan was among the earliest evidence for the presence of sugars on cell surfaces and their potential roles as identity markers, an accepted theme in modern glycobiology. It took a while, however, before the counterreceptors for surface sugars, that is, the endogenous lectins that recognize these sugars, were identified, the first being the mammalian hepatic asialoglycoprotein receptor to be described later.
The ability of plant agglutinins to distinguish between erythrocytes of different blood types led Boyd and Shapleigh (1954) to propose for them the name lectins, from the Latin legere, to pick out or choose. This term was generalized by us to embrace all sugar-specific agglutinins of nonimmune origin, irrespective of source and blood type specificity (Sharon and Lis, 1972
).
![]() |
Mitogenic stimulation of lymphocytes and agglutination of cancer cells |
---|
The second discovery was made by Joseph C. Aub at the Massachusetts General Hospital in Boston (Aub et al., 1963, 1965
). He found that wheat germ agglutinin (WGA) has the ability to preferentially agglutinate malignant cells. This was followed by the reports of Max M. Burger at Princeton University and Leo Sachs and Michael Inbar at the Weizmann Institute (Rehovot) that concanavalin A exhibits the same ability. Together with Sachs and Ben-Ami Sela, we subsequently found that soybean agglutinin (SBA) also possesses the same property. Such investigations provided early evidence that changes in cell surface sugars are associated with the development of cancer and led to the assumption that high susceptibility to agglutination by lectins was a property shared by all malignant cells. Unfortunately, this is now known not to be generally true.
![]() |
Lectins galore |
---|
|
![]() |
From primary to 3D structures |
---|
The availability of the primary structure of numerous lectins allowed the identification of homologies between the sequences of lectins from taxonomically related sources, as originally demonstrated for the legume lectins by one of us (N.S.) in collaboration with Donny Strosberg at the Free University of Brussels (Foriers et al., 1977). By the end of the following decade, homologies were found also for lectins from other families, such as the galectins and the C-type (Ca2+ requiring) lectins (Drickamer, 1988
).
During the past few years, the number of lectin primary and 3D structures has increase dramatically, with some 200 of the latter having been elucidated (www.cermav.cnrs.fr/lectines). In addition, many structures of lectincarbohydrate complexes have been solved. Quite surprisingly, remarkable similarities have been noticed between the tertiary structures of lectins from diverse sources, in spite of the lack of primary sequence similarities (Figure 1). One such common tertiary structure, first observed in the legume lectins, and referred to as the lectin fold, consists characteristically of an elaborate jelly roll, derived from antiparallel ß-strands, arranged as two ß-sheets (Srinivasan et al., 1996). This fold has been found in the legume lectins, the galectins, and in several other animal lectins, such as the pentraxins (Crennel et al., 1994
) and ERGIC-53 (Itin et al., 1996
; Velloso et al., 2002
), as well as in nonlectin molecules, for example, several glycosidases, among them Vibrio cholerae sialidase.
|
![]() |
Carbohydrate recognition domains |
---|
The majority of the CTLs are large, asymmetric transmembrane glycoproteins, in which the CRD is attached to a variable number of structurally and functionally different polypeptide domains. In contrast, the galectins are generally small, soluble, nonglycosylated proteins and, unlike the CTLs, do not require Ca2+ for their activity. Members of the CTL superfamily are grouped into three familiesselectins (the most celebrated one), collectins, and endocytic lectins. The story of the selectins started with attempts to elucidate the molecular basis of lymphocyte homing. These attempts greatly benefited from the availability of an in vitro assay for measuring the interaction of lymphocytes with postcapillary high-endothelial venules (HEVs), a known site of lymphocyte exit from the blood stream (Stamper and Woodruff, 1977). Using this assay, which reflects the in vivo homing of lymphocytes, Eugene C. Butcher and colleagues at Stanford University obtained a monoclonal antibody (MEL-14) against a murine lymphocyte antigen (Gallatin et al., 1983
). The antibody inhibited the binding of the lymphocytes to HEV in vitro and their homing in vivo, suggesting that the MEL-14 antigen has a direct role in these phenomena. From inhibition experiments of the lymphocyte-HEV binding, Steven D. Rosen and Lloyd M Stoolman at the University of California, San Francisco, have concluded that sugars of the endothelial cell might also be involved in this binding and that the lymphocytes should have a membrane-bound lectin with specificity for fucose and Man-6-P (Stoolman et al., 1984
). This lectin was subsequently shown to be identical with the MEL-14 antigen.
In 1987 Bevilacqua and co-workers of Harvard Medical School have developed two monoclonal antibodies that identified a second cell-surface antigen, designated ELAM (endothelial-leukocyte adhesion molecule)-1, expressed on stimulated human endothelial cells but not on unstimulated ones (Bevilacqua et al., 1987). Another vascular cell adhesion molecule was originally isolated from activated platelets independently by Rodger McEver at the Oklahoma Medical Research Foundation, Oklahoma City (McEver and Martin, 1984
) and by Bruce and Barbara C. Furie at Tufts University, Boston (Berman et al., 1986
; Hsu-Lin et al., 1984
), and designated GPM-140 and PADGEM, respectively.
These three cell adhesion molecules, collectively known for a while as LEC-CAMS, were identified as a discrete family of CTLs after the virtually simultaneous publication in 1989 of their primary sequences (Bevilacqua et al., 1989; Johnston et al., 1989
; Lasky et al., 1989
; Siegelman et al., 1989
); these go now under the names L-selectin, E-selectin, and P-selectin, respectively (reviewed in Lasky, 1995
). They were all shown to have a similar domain structure, with an extracellular part that consists of an amino terminal CRD, an epidermal growth factorlike domain, and several short repeating units related to complement-binding protein. They bind specifically to the trisaccharide NeuAc
(2-3)Galß(1-4)[Fuc
(1-3)]GlcNAc, known as sialyl-Lewisx (siaLex in brief) and its positional isomer, NeuAc
(2-3)Galß(1-3)[Fuc
(1-4)]GlcNAc (siaLea), with both fucose and sialic acid required for binding (Brandley et al., 1990
; Stoolman, 1989
). The selectins recognize the carbohydrate ligands only when the latter are present on particular glycoproteins, such as cell surface mucins, pointing to the role of the carrier molecule in lectin-carbohydrate interactions; one of the best characterized of such carriers is the P-selectin glycoprotein ligand (Moore et al., 1992
).
The paradigm of the endocytic lectins is the mammalian hepatic asialoglycoprotein receptor already mentioned. The collectins, represented by the soluble mannose-binding proteins of mammalian serum and liver, first detected by chance as a contaminant of a preparation of -mannosidase from human liver (Robinson et al., 1975
), subsequently purified and characterized by Toshiaki Kawasaki and Ikuo Yamashina at Kyoto University, Japan (Kawasaki et al., 1978
; Kozutsumi et al., 1980
), are characterized by an NH2-terminal collagen-like stretch of repeating Gly-X-Y- triplets (where X and Y are any amino acid). The structural unit of the mannose-binding proteins is a trimer of identical subunits with a triple-stranded collagen helix and three CRDs (Weis and Drickamer, 1994
). This arrangement of CRDs at a fixed spacing has important biological implications, to be discussed later.
A different kind of CRD has been identified in the siglecs. This family of sialic acidbinding Ig-like lectins, a member of the Ig superfamily, was discovered when the cloning of a macrophage lectin-like adhesion molecule named sialoadhesin (siglec-1) revealed striking structural similarities to a B cell restricted member of the Ig superfamily, CD22 (siglec-2) and to two other members of the Ig superfamily, CD33 (siglec-3) and the myelin-associated glycoprotein (siglec-4) (Crocker et al., 1994). Members of this family, 11 of which have been identified in humans, are type 1 transmembrane proteins with an extracellular part consisting of a CRD-containing N-terminal V-set Ig-like domain, followed by variable numbers of C2-set Ig-like domains. Except for myelin-associated glycoprotein (siglec-4), exclusively expressed in the nervous system, they are all found on cells of the hematopoietic system. Each siglec has a distinct expression pattern in different cell types, indicating that they perform highly specific functions.
A recent addition to the growing list of mammalian lectins is dectin-1, a ß-glucan receptor, identified by Gordon Brown and Siamon Gordon (2001) at Oxford by screening a cDNA library of a macrophage cell line with zymosan. It is a small type II transmembrane receptor containing one CRD, which recognizes ß1,3 and/or ß1,6-glucans and intact yeasts.
![]() |
In protection and symbiosis |
---|
Probably the earliest publication on the insecticidal action of lectins came in 1976 from the laboratory of Irvin E. Liener at the University of Minnesota, at St. Paul (Minnesota) in which it was reported that feeding bruchid beetles with a diet containing the black bean lectin resulted in the death of the bruchid larvae (Janzen et al., 1976). On this basis the authors concluded that the major role of lectins in legumes is to protect them from attack by insect seed predators. In subsequent studies, several other lectins were shown to be insecticidal, among them WGA, Galanthus nivalis lectin and jacalin.
The proposal that lectins may be involved in the protection of plants against pathogenic microorganisms was originally based on the observation made at Rehovot that WGA, PNA, and SBA inhibited the sporulation and growth of fungi such as Trichoderma viride, Penicilium notatum, and Aspergillus niger (see Barkai-Golan et al., 1976). Potato lectin was subsequently shown to act in a similar manner on Botrytis cinerea, another fungal phytopathogen. In an extensive study, 11 purified lectins representing the major carbohydrate specificity groups were all found to cause growth disruption during germination of spores of Neurospora crassa, Aspergillus amstelodami, and Botryodiplodia theobromae (Brambl and Gade, 1985). It was also shown that recombinant Urtica dioica agglutinin that has a similar specificity to that of WGA (Broekaert et al., 1989
) inhibited the growth of fungal phytopathogens.
The idea that lectins are responsible for the specific association between nitrogen-fixing rhizobia and leguminous plants, which provides the plant with the needed nitrogen, was advanced nearly three decades ago (Bohlool and Schmidt, 1974; Hamblin and Kent, 1973
). It was based on the finding that a lectin from a particular legume bound in a carbohydrate-specific manner to the surface polysaccharides or lipopolysaccharides of the corresponding rhizobial species but not to bacteria that are symbionts of other legumes. For instance, SBA agglutinated most strains of Bradyrhizobium japonicum that nodulate soybeans but not nonnodulating bradyrhizobial strains. The suggestion has therefore been made that rhizobial attachment to plant roots occurs by interaction between the bacterial surface carbohydrates and lectins present in the roots of the leguminous plants. This became known as the lectin recognition hypothesis, which is still the subject of controversy, because of the lack of unequivocal evidence and of some inconsistencies. Thus for most hostsymbiont systems examined, there is no proof for the presence of lectins and their ligands on plant roots and bacteria, respectively, at precisely the right time and location. Moreover, the correlation between the specificity of the host lectin and its ability to recognize the nodulating bacteria of that host is not very strict. Also, several lines of soybeans with no detectable lectin in their seeds or vegetative tissues were nodulated normally by the corresponding rhizobial symbiont.
Application of the techniques of molecular genetics gave results that bolstered the lectin recognition hypothesis but did not fully settle the controversy (reviewed by Kijne, 1996; Hirsch, 1999
).
Recently, a variant of the lectin recognition hypothesis has been proposed, that postulates that the host-specific attachment of the rhizobium is achieved through the interaction between species-specific lipo-chitooligosaccharide signal molecules produced by the bacteria, named nodulation factors (Nods), and a new type of a plant root lectin found in different leguminous plants but not in plants of different families (Kalsi and Etzler, 2000).
![]() |
Recognition molecules |
---|
|
|
Another key finding was made in 1979, when our group, together with others, demonstrated that urinary tract infection in mice by mannose-specific Escherichia coli could be prevented by methyl -D-mannoside (Aronson et al., 1979
). It was the first direct evidence for the involvement of bacterial lectins in the initiation of infection, the basis for the present attempts in academia and industry, to apply carbohydrates for antiadhesion therapy of such diseases (reviewed by Mulvey et al., 2001
).
Together with Itzhak Ofek, we demonstrated at the same time that the mannose-specific bacterial surface lectins may also mediate attachment of the bacteria to phagocytic cells in the absence of opsonins, leading to engulfment and killing of the bacteria. This process, another example of innate immunity, which we named lectinophagocytosis, may be of importance in the clearance of bacteria from nonimmune patients or from opsonin-poor sites, such as renal medulla or the peritoneal cavity (Ofek and Sharon, 1988). Additional lectins have been implicated in innate immunity. A prominent example is the mannose-specific receptor present on the surface of macrophages; it binds infectious organisms that expose mannose-containing glycans on their surface, leading to their ingestion and killing. Another, recently discovered one, is dectin-1, specific for ß1,3 and/or ß1,6-glucans, present on fungi.
A similar function, albeit by a different mechanism, is performed by the soluble mannose-binding lectins (MBLs) of mammalian serum and liver (Epstein et al., 1996; Turner, 1996
), These proteins bind to oligomannosides of infectious microorganisms, causing activation of complement without participation of antibody, and subsequent lysis of the pathogens, thus acting in innate immunity. The spatial arrangement of the CRDs in the MBLs provides a structural basis for their ability to bind ligands with repetitive, mannose-rich structures, such as found on fungal and microbial surfaces, but not to the oligomannose units of mammalian glycoproteins (Weis and Drickamer, 1994
).
The discovery of the selectins and the demonstration that they play a crucial role in the control of lymphocyte homing and of leukocyte trafficking to sites of inflammation was a landmark in lectin research. Indeed, the selectins provide the best paradigm for the role of sugarlectin interactions in biological recognition. They mediate the binding of leukocytes to endothelial cells and thereby initiate a rolling phase, in which the lectins interact transiently with glycan ligands, leading eventually to their extravasation. Prevention of adverse inflammatory reactions by inhibition of leukocyteendothelium interactions, another application of antiadhesion therapy, has become a major aim of the biomedical and pharmacological industry. There are also indications that the selectins may function in the spread of cancer cells from the main tumor to other sites in the body and that by blocking their sugar-binding sites it may be possible to prevent the formation of metastases.
From the late 1980s, evidence started to accumulate that several lectins of different types direct intracellular glycoprotein traffic, by acting as chaperones and sorting receptors in the secretory pathway. Calnexin, a membrane-bound lectin of the endoplasmic reticulum (ER), functions in parallel with calreticulin, its soluble homolog, as part of a quality control system that ensures proper folding of glycoproteins destined to the cell surface. The mannose-specific intracellular lectin, ERGIC-53, first identified as a resident of the ERGolgi intermediate compartment protein (Schweizer et al., 1988) carries a specific subset of nascent glycoproteins between the two compartments. Two distinct mannose-6-phospate receptors, the only members of the P-type lectin family, mediate the targeting of newly synthesized hydrolases from the rough ER to the lysosomes (Hoflack and Kornfeld, 1985
). Both receptors bind their ligands, oligosaccharides bearing terminal Man-6-P residues, most efficiently at pH 67, allowing them to interact with hydrolases decorated with such oligosaccharides in the trans-Golgi network, and to release them in the more acidic environment of the lysosomes.
The galectins are believed to act as modulators of cellsubstratum interactions and to be essential for the normal differentiation and growth of all multicellular animals. They are capable of inducing cell proliferation, cell arrest, or apoptosis (physiological cell death) and have been implicated in organ morphogenesis, tumor cell metastasis, leukocyte trafficking, immune response, and inflammation, as well as recognition of extracellular matrix.
![]() |
Epilogue |
---|
![]() |
Footnotes |
---|
![]() |
Abbreviations |
---|
![]() |
References |
---|
Agrawal, B.B.I. and Goldstein, I.J. (1967) Specific binding of concanvalin A to cross-linked dextran gels. Biochem. J., 96, 23C15C.
Aronson, M., Medalia, O., Schori, L., Mirelman, D., Sharon, N., and Ofek, I. (1979) Prevention of colonization of the urinary tract of mice with Escherichia coli by blocking of bacterial adherence with methyl -D-mannopyranoside. J. Infect. Dis., 139, 329332.[ISI][Medline]
Ashwell, G. and Morell, A.G. (1972) Membrane glycoproteins and recognition phenomena. Trends Biochem. Sci., 2, 7678.[CrossRef]
Ashwell, G. and Morell, A.G. (1974) The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv. Enzymol. Relat. Areas Mol. Biol., 41, 99128.[ISI][Medline]
Aub, J.C., Tieslau, C., and Lankester, A. (1963) Reactions of normal and tumor cell to enzymes. I. Wheat-germ lipase and associated mucopolysaccharides. Proc. Natl Acad. Sci. USA, 50, 613619.[ISI][Medline]
Aub, J.C., Sanford, B.H., and Cote, M.N. (1965) Studies on reactivity of tumor and normal cells to a wheat germ agglutinin. Proc. Natl Acad. Sci. USA, 54, 396399.[ISI][Medline]
Barkai-Golan, R, Mirelman, D., and Sharon, N. (1978) Studies on growth inhibition by lectins of Penicillia and Aspergilli. Arch. Microbiol., 116, 119121.[ISI][Medline]
Barondes, S.H., Castronovo, V., Cooper, D.N.W., and others. (1994) Galectinsa family of beta-galactoside-binding lectins. Cell, 76, 597598.[ISI][Medline]
Berman, C.L., Yeo, E.L., Wencel-Drake, J.D., Furie, B.C., Ginsberg, M.H., and Furie, B. (1986) A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein. J. Clin. Invest., 78, 130137.[ISI][Medline]
Bevilacqua, M.P., Pober, J.S., Mendrick, D.L., Cotran, R.S., and Gimbrone, M.A. Jr. (1987) Identification of an inducible endothelial-leukocyte adhesion molecule. Proc. Natl Acad. Sci. USA, 84, 92389242.[Abstract]
Bevilacqua, M.P., Stengelin, S., Gimbrone, M.A. Jr., and Seed, B. (1989) Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science, 243, 11601165.[ISI][Medline]
Bohlool, B.B. and Schmidt, E.L. (1974) Lectins: a possible basis for specificity in the Rhizobium-legume root module symbiosis. Science, 188, 269271.
Boyd, W.C. and Shapleigh, E. (1954) Specific precipitation activity of plant agglutinins (lectins). Science, 119, 419.
Brambl, R. and Gade, W. (1985) Plant seed lectins disrupt growth of germinating fungal spores. Physiol. Plant, 64, 402408.[ISI]
Brandley, B.K., Swiedler, S.J., and Robbins, P.W. (1990) Carbohydrate ligands of the LEC cell adhesion molecules. Cell, 63, 861863.[ISI][Medline]
Broekaert, W.F., Van Parijs, J., Leyns, F., Joos, H., and Peumans, W.J. (1989) A chitin-binding lectin from stinging nettle rhizomes with antifungal properties. Science, 245, 11001102.[ISI]
Brown, G.D. and Gordon, S. (2001) Immune recognition: a new receptor for beta glucans. Nature, 413, 3637.[CrossRef][ISI][Medline]
Crennel, S., Garman, E., Laver, G., Vimr, E., and Taylor, G. (1994) Crystal structure of Vibrio cholerae neuraminidase reveals dual lectin-like domains in addition to the catalytic domain. Structure, 2, 535544.[ISI][Medline]
Crocker, P.R., Mucklow, S., Bouckson, V., McWilliam, A., Willis, A.C., Gordon, S., Milon, G., Kelm, S., and Bradfield, P. (1994) Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J., 13, 44904503.[Abstract]
Drickamer, K. (1988) Two distinct classes of carbohydrate-recognition domains in animal lectins. J. Biol. Chem., 263, 95579560.
Edelman, G.M., Cunningham, B.A., Reeke, G.N. Jr., Becker, J.W., Waxdal, M.J., and Wang, J.L. (1972) The covalent and three-dimensional structure of concanavalin A. Proc. Natl Acad. Sci. USA, 69, 25802584.[Abstract]
Epstein, J., Eichbaum, Q., Sheriff, S., and Ezekowitz, R.A. (1996) The collectins in innate immunity. Curr. Opin. Immunol., 8, 2935.[CrossRef][ISI][Medline]
Etzler, M.E. (1986) Distribution and function of plant lectins. In Liener, I.E., Sharon, N., and Goldstein, I.J. (Eds.), The lectins: properties, functions and applications in biology and medicine. Academic Press, Orlando, FL, pp. 371435.
Foriers, A., Wuilmart, C., Sharon, N., and Strosberg, A.D. (1977) Extensive sequence homologies among lectins from leguminous plants. Biochem. Biophys. Res. Commun., 75, 980986.[ISI][Medline]
Franz, H. (1988) The ricin story. Adv. Lectin Res., 1, 1025.
Gallatin, W.M., Weissman, I.L., and Butcher, E.C. (1983) A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature, 304, 3034.[ISI][Medline]
Hamblin, J. and Kent, S.P. (1973) Possible role of phytohaemagglutinin in Phaseolus vulgaris L. Nat. New Biol., 245, 2830.[ISI][Medline]
Hammarström, S. and Kabat, E.A. (1969). Purification and characterization of a blood-group A reactive hemagglutinin from the snail Helix pomatia and a study of its combining site. Biochemistry, 8, 26962705.[ISI][Medline]
Hardman, K.D. and Ainsworth, C.F. (1972) Structure of concanavalin A at 2.4-Å resolution. Biochemistry, 11, 49104919.[ISI][Medline]
Hirsch, A.M. (1999) Role of lectins and rhizobial exopolysaccharides in legume nodulation. Curr. Opin. Plant Biol., 2, 320326.[CrossRef][ISI][Medline]
Hoflack, B. and Kornfeld, S. (1985) Lysosomal enzyme binding to mouse P388D1 macrophage membranes lacking the 215-kDa mannose 6-phosphate receptor: evidence for the existence of a second mannose 6-phosphate receptor. Proc. Natl Acad. Sci. USA, 82, 44284432.[Abstract]
Hsu-Lin, S., Berman, C.L., Furie, B.C., August, D., and Furie, B. (1984) A platelet membrane protein expressed during platelet activation and secretion. Studies using a monoclonal antibody specific for thrombin-activated platelets. J. Biol. Chem., 259, 91219126.
Hudgin, R.L., Pricer, W.E. Jr., Ashwell, G., Stockert, R.J., and Morell, A.G. (1974) The isolation and properties of a rabbit liver binding protein specific for asialoglycoproteins. J. Biol. Chem., 249, 55365543.
Itin, C., Roche, A.C., Monsigny, M., and Hauri, H.P. (1996) ERGIC-53 is a functional mannose-selective and calcium-dependent human homologue of leguminous lectins. Mol. Biol. Cell, 7, 483493.[Abstract]
Janzen, D.H., Juster, H.B., and Liener I.E. (1976) Insecticidal action of the phytohemagglutinin in black beans on a bruchid beetle. Science, 192, 795796.[ISI][Medline]
Johnston, G.I., Cook, R.G., and McEver, R.P. (1989) Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell, 56, 10331044.[ISI][Medline]
Kalsi, G. and Etzler, M.E. (2000) Localization of a Nod factor-binding protein in legume roots and factors influencing its distribution and expression. Plant Physiol., 124, 10391048.
Kaplan, A., Achord, D.T., and Sly, W.S. (1977) Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc. Natl Acad. Sci. USA, 74, 10161030.[Abstract]
Kawasaki, T., Etoh, R., and Yamashina, I. (1978) Isolation and characterization of a mannan-binding protein from rabbit liver. Biochem Biophys. Res. Commun., 81, 10181024.[ISI][Medline]
Kijne, J.W. (1996) Functions of plant lectins. Chemtracts Biochem. Mol. Biol., 6, 180187.
Kocourek, J. (1986) Historical background. In Liener, I.E., Sharon, N., and Goldstein, I.J. (Eds.), The lectins: properties functions and applications in biology and medicine. Academic Press, Orlando, FL, pp. 132.
Kozutsumi, Y., Kawasaki, T., and Yamashina, I. (1980) Isolation and characterization of a mannan-binding protein from rabbit serum. Biochem. Biophys. Res. Commun., 95, 658664.[ISI][Medline]
Landsteiner, K. (1936) The specificity of serological reactions. Baillière, Tindall and Cox, London, p. 5.
Landsteiner, K. and Raubitschek, H. (1907) Beobachtungen über Hämolyse und Hämagglutination. Zbl. Bakt. I. Abt. Orig., 45, 600607.
Lasky, L.A. (1995) Selectin-carbohydrate interactions and the initiation of the inflammatory response. Annu. Rev. Biochem., 64, 113139.[CrossRef][ISI][Medline]
Lasky, L.A., Singer, M.S., Yednock, T.A., Dowbenko, D., Fennie, C., Rodriguez, H., Nguyen, T., Stachel, S., and Rosen, S.D. (1989) Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell, 56, 10451055.[ISI][Medline]
Mäkelä O. (1957) Studies in hemagglutinins of Leguminosae seeds. Ann. Med. Exp. Fenn., Suppl. 11.
Marchalonis, J.J. and Edelman, G.M. (1968) Isolation and characterization of a hemagglutinin from Limulus polyphemus. J. Mol. Biol. 32, 453465.[ISI][Medline]
McEver, R.P. and Martin, M.N. (1984) A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J. Biol. Chem., 259, 97999804.
Moore, K.L., Stults, N.L., Diaz, S., Smith, D.F., Cummings, R.D., Varki, A., and McEver, R.P. (1992) Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J. Cell Biol., 118, 445456.[Abstract]
Morgan, D.A., Ruscetti, F.W., and Gallo, R. (1976) Selective in vitro growth of T lymphocytes from normal human bone marrows. Science, 193, 10071008.[ISI][Medline]
Morgan, W.T. and Watkins, W.M. (2000) Unraveling the biochemical basis of blood group ABO and Lewis antigenic specificity. Glycoconj. J., 17, 501530.[CrossRef][ISI][Medline]
Nowell, P.C. (1960) Phytohemagglutinin: an initiator of mitosis in culture of animal and human leukocytes. Cancer Res., 20, 462466.[ISI][Medline]
Mulvey, G., Kitov, P., Marcato, P., Bundle, D.R., and Armstrong, G.D. (2001) Glycan mimicry as a basis for novel anti-infective drugs. Biochimie, 83, 841847.[CrossRef][ISI][Medline]
Ofek, I. and Sharon, N. (1988) Lectinophagocytosis: a molecular mechanism of recognition between cell surface sugars and lectins in the phagocytosis of bacteria. Infect. Immun., 56, 539547.[ISI][Medline]
Ofek, I., Beachey, E.H., and Sharon, N. (1978) Surface sugars of animal cells as determinants of recognition in bacterial adherence. Trends Biochem. Sci., 3, 159160.[ISI]
Robinson, D., Phillips, N.C., and Winchester, B. (1975) Affinity chromatography of human liver -D-mannosidase. FEBS Lett., 53, 110112.[CrossRef][ISI][Medline]
Schweizer, A., Fransen, J.A., Bachi, T., Ginsel, L., and Hauri, H.P. (1988) Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus. J. Cell Biol., 107, 16431653.[Abstract]
Sharon, N. (1993) Lectin-carbohydrate complexes of plants and animals: an atomic view. Trends Biochem. Sci., 18, 221226.[CrossRef][ISI][Medline]
Sharon, N. and Lis, H. (1972) Lectins: cell-agglutinating and sugar-specific proteins. Science, 177, 949959.[ISI][Medline]
Sharon, N. and Lis, H. (2003) Lectins, 2nd ed. Kluwer Scientific Publishers, Amsterdam.
Sharon, N., Lis, H., and Lotan, R. (1974) On the structural diversity of lectins. Coll. Int. CNRS, 221, 693709.
Siegelman, M.H., van de Rijn, M., and Weissman, I.L. (1989) Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains. Science, 243, 11651172.[ISI][Medline]
Springer, G.F. and Desai, P.R. (1971) Monosaccharides as specific precipitinogens of eel anti-human blood group H (O) antibody. Biochemistry, 10, 37493760.[ISI][Medline]
Srinivasan, N., Rufino, S.D., Pepys, M.B., Wood, S., and Blundell, T.L. (1996) A superfamily of proteins with the lectin fold. Chemtracts Biochem. Mol. Biol., 6, 149164.
Stamper, H.B. Jr. and Woodruff, J.J. (1977) An in vitro model of lymphocyte homing. I. Characterization of the interaction between thoracic duct lymphocytes and specialized high-endothelial venules of lymph nodes. J. Immunol., 119, 772780.[ISI][Medline]
Stockert, R.J., Morell, A.G., and Scheinberg, I.H. (1974) Mammalian hepatic lectin. Science, 186, 365366.[ISI][Medline]
Stoolman, L.M. (1989) Adhesion molecules controlling lymphocyte migration. Cell, 56, 907910.[ISI][Medline]
Stoolman, L.M., Tenforde, T.S., and Rosen, S.D. (1984) Phosphomannosyl receptors may participate in the adhesive interaction between lymphocytes and high endothelial venules. J. Cell Biol., 99, 15351540.[Abstract]
Sumner, J.B. and Howell, S.F. (1936) The identification of the hemagglutinin of the jack bean with concanavalin A. J. Bacteriol., 32, 227237.
Teichberg, V.I., Silman, I., Beitsch, D.D., and Resheff, G. (1975) A ß-D-galactoside binding protein from electric organ tissue of Electrophorus electricus. Proc. Natl Acad. Sci. USA, 72, 13831387.[Abstract]
Turner, M.W. (1996) Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol. Today, 17, 532540.[CrossRef][ISI][Medline]
Velloso, L.M., Svensson, K., Schneider, G., Pettersson, R.F., and Lindqvist, Y. (2002) Crystal structure of the carbohydrate recognition domain of p58/ERGIC-53, a protein involved in glycoprotein export from the endoplasmic reticulum. J. Biol. Chem., 277, 1597915984.
Watkins, W.M. and Morgan, W.T.J. (1952) Neutralization of the anti-H agglutinin in eel serum by simple sugars. Nature, 169, 825826.[ISI][Medline]
Weis, W.I. and Drickamer, K. (1994) Trimeric structure of a C-type mannose-binding protein. Structure, 2, 12271240.[ISI][Medline]
Wright, C.S. (1977). The crystal structure of wheat germ agglutinin at 22 Å resolution. J. Mol. Biol., 111, 439457.[ISI][Medline]