Abstract
UDP-Gal:lactosylceramide alpha 1,4-galactosyltransferase (A4GALT) catalyzes the transfer of galactose from UDP-galactose to lactosylceramide (Taga et al. 1995) as shown in Fig. 14.1. The product is called globotriaosylceramide (Gb3) or CD77. This structure is a molecule locating at the starting point for the synthesis of globo-series glycosphingolipids. Gb3 and more complex glycosphingolipids in this series are expressed in relatively restricted tissues and cells in our bodies, i.e., erythrocytes, kidney, endothelium, and some population of germinal center B lymphocytes (Klein et al. 1983). In human cancers, Burkitt’s lymphomas characteristically express Gb3 (Wiels et al. 1981).
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References
Boyd B, Lingwood C (1989) Verotoxin receptor glycolipid in human renal tissue. Nephron 51:207–210
Chang WW, Lee CH, Lee P, Lin J, Hsu CW, Hung JT, Lin JJ, Yu JC, Shao LE, Yu J, Wong CH, Yu AL (2008) Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis. Proc Natl Acad Sci USA 105:11667–11672
Fujii Y, Numata S, Nakamura Y, Honda T, Furukawa K, Urano T, Wiels J, Uchikawa M, Ozaki N, Matsuo S, Sugiura Y, Furukawa K (2005) Murine glycosyltransferases responsible for the expression of globo-series glycolipids: cDNA structures, mRNA expression, and distribution of their products. Glycobiology 15:1257–1267
Furukawa K, Iwamura K, Uchikawa M, Sojka BN, Wiels J, Okajima T, Urano T, Furukawa K (2000) Molecular basis for the p phenotype: identification of distinct and multiple mutations in the a1,4-galactosyltransferase gene in Swedish and Japanese individuals. J Biol Chem 275:37752–37756
Furukawa K, Yokoyama K, Sato T, Wiels J, Hirayama Y, Ohta M, Furukawa K (2002) Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells: implication in the sensitivity to verotoxins. J Biol Chem 277:11247–11254
Iwamura K, Furukawa K, Uchikawa M, Birgitta NS, Kojima Y, Wiels J, Urano T, Furukawa K (2003) The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene: a clue to the solution of the P1/P2/p puzzle. J Biol Chem 278:44429–44438
Jacewick M, Clausen H, Nudelman E, Donohue-Rolfe A, Keusch GT (1986) Pathogenesis of shigella diarrhea. XI. Isolation of a shigella toxin-binding glycolipid from rabbit jejunum and HeLa cells and its identification as globotriaosylceramide. J Exp Med 163:1391–1404
Karlsson KA (1995) Microbial recognition of target-cell glycoconjugates. Curr Opin Struct Biol 5:622–635
Keusch JJ, Manzella SM, Nyame KA, Cummings RD, Baenziger JU (2000) Expression cloning of a new member of the ABO blood group glycosyltransferases, iGb3 synthase, that directs the synthesis of isoglobo-glycosphingolipids. J Biol Chem 275:25308–25314
Klein G, Manneborg-Sandlund A, Ehlin-Henriksson B, Godal T, Wiels J, Tursz T (1983) Expression of the BLA antigen, defined by the monoclonal 38.13 antibody, on Burkitt lymphoma lines, lymphoblastoid cell lines, their hybrids and other B-cell lymphomas and leukemias. Int J Cancer 31:535–542
Kojima Y, Fukumoto S, Furukawa K, Okajima T, Wiels J, Yokoyama K, Suzuki Y, Urano T, Ohta M, Furukawa K (2000) Molecular cloning of globotriaosyl-ceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem 275:15152–15156
Kondo Y, Ikeda K, Tokuda N, Nishitani C, Ohto U, Akashi-Takamura S, Ito Y, Uchikawa M, Kuroki Y, Taguchi R, Miyake K, Zhang Q, Furukawa K, Furukawa K (2013) TLR4-MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide. Proc Natl Acad Sci USA 110:4714–4719. doi:10.1073/pnas.1218508110
Kovbasnjuk O, Mourtazina R, Baibakov B, Wang T, Elowsky C, Choti MA, Kane A, Donowitz M (2005) The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proc Natl Acad Sci USA 102:19087
Lund B, Lindberg FP, Baga M, Normark S (1985) Globoside-specific adhesins of uropathogenic Escherichia coli are encoded by similar trans-complementable gene clusters. J Bacteriol 162:1293–1301
Okuda T, Tokuda N, Numata S, Ito M, Ohta M, Kawamura K, Wiels J, Urano T, Tajima O, Furukawa K, Furukawa K (2006) Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281:10230–10235
Römer W, Berland L, Chambon V, Gaus K, Windschiegl B, Tenza D, Aly MR, Fraisier V, Florent JC, Perrais D, Lamaze C, Raposo G, Steinem C, Sens P, Bassereau P, Johannes L (2007) Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450:670–675
Satoh M, Handa K, Saito S, Tokuyama S, Ito A, Miyao N, Orikasa S, Hakomori S (1996) Disialosyl galactosylgloboside as an adhesion molecule expressed on renal cell carcinoma and its relationship to metastatic potential. Cancer Res 56:1932–1938
Satoh M, Nejad FM, Ohtani H, Ito A, Ohyama C, Saito S, Orikasa S, Hakomori S (2000) Association of renal cell carcinoma antigen, disialylgalactosylgloboside, with c-Src and Rho A in clustered domains at the surface membrane. Int J Oncol 16:529–536
Schrump DS, Furukawa K, Yamaguchi H, Lloyd KO, Old LJ (1988) Recognition of galactosylgloboside by monoclonal antibodies derived from patients with primary lung cancer. Proc Natl Acad Sci USA 85:4441–4445
Steffensen R, Carlier K, Wiels J, Levery SB, Stroud M, Cedergren B, Nilsson Sojka B, Bennett EP, Jersild C, Clausen H (2000) Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype. J Biol Chem 275:16723–16729
Taga S, Mangeney M, Tursz T, Wiels J (1995) Differential regulation of glycosphingolipid biosynthesis in phenotypically distinct Burkitt’s lymphoma cell lines. Int J Cancer 61:261–267
Wenk J, Andrews PW, Casper J, Hata J, Pera MF, von Keitz A, Damjanov I, Fenderson BA (1994) ES marker glycolipids of germ cell tumors: extended globo-series glycolipids are a hallmark of human embryonal carcinoma cells. Int J Cancer 58:108–115
Wiels J, Fellous M, Tursz T (1981) Monoclonal antibody against a Burkitt lymphoma-associated antigen. Proc Natl Acad Sci USA 78:6485–6488
Yamakawa T (1984) Wonders in glycolipids – a historical view. Adv Exp Med Biol 174:3–13
Yamakawa T, Yokoyama S, Handa N (1963) Chemistry of lipids of posthemolytic residue or stroma of erythrocytes. XI. Structure of globoside, the main mucolipid of human erythrocytes. J Biochem 53:28–36
Yamakawa T, Yokoyama S, Kiso N (1962) Structure of main globoside of human erythrocytes. J Biochem 52:228–229
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Furukawa, K., Kondo, Y., Furukawa, K. (2014). UDP-Gal: Lactosylceramide Alpha 1,4-Galactosyltransferase (A4GALT). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_33
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DOI: https://doi.org/10.1007/978-4-431-54240-7_33
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