Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hodgkin-associated Ki-1 antigen occurs in two different molecular forms. The 120-kDa membrane-associated form is a phosphorylated glycoprotein, which is derived from a non-phosphorylated intracellular 84-kDa apoprotein that is co-translationally N-glycosylated with a carbohydrate portion of 6 kDa. The other form of the Ki-1 antigen is a non-glycosylated phosphoprotein of 57 kDa which only occurs intracellularly. Both forms of the antigen are phosphorylated at serine residues. Enzymatic cleavage with sialidase reduced the 120-kDa membrane antigen by about 15 kDa, while its 90-kDa precursor and the 57-kDa intracellular form of the Ki-1 antigen remained unaltered. Pulse-chase experiments revealed that the 57-kDa and 90/120-kDa molecules are synthesized independently of each other. Four to eight hours after synthesis, the degradation of the 120-kDa molecule to a 105-kDa membrane-associated intermediate begins. This is further processed and appears in the cell supernate as a 90-kDa molecule. Hodgkin's disease-derived, Epstein-Barr virus-transformed cell lines and the acute T cell leukemia line MOLT-4 contain both forms of the Ki-1 antigen, whereas only the 57-kDa intracellular antigen is expressed in U266/B1 myeloma cells, in the Burkitt lymphoma cell lines Raji and Daudi and in acute promyelocytic HL-60 leukemia cells.
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PMID:The Hodgkin-associated Ki-1 antigen exists in an intracellular and a membrane-bound form. 254 29

In our previous study, a Burkitt lymphoma-associated antigen defined by a monoclonal antibody, designated 38.13, was characterized as globotriaosylceramide (Gb3, Gal alpha 1----4 Gal beta 1----4 Glc beta 1----1 Cer) (Nudelman, E., Kannagi, R., Hakomori, S., Parsons, M., Lipinski, M., Wiels, J., Fellous, M., and Tursz, T. (1983) Science (Wash. D.C.) 220, 509-511). Consequently, we have studied the enzymatic basis and organization of Gb3 expression in Burkitt as compared with non-Burkitt lymphoblastoid cell lines. Burkitt lymphoma cell lines (Ramos, Daudi, Put) were characterized by a high chemical quantity of Gb3, high enzyme activity for synthesis of Gb3 (UDP-Gal:LacCer alpha-galactosyltransferase), and a high degree of surface exposure of Gb3, as determined by galactose oxidase/NaB[3H]4 and by cytofluorometry with the monoclonal antibody to Gb3 (38.13). Non-Burkitt lymphoblastoid cell lines (Priess, Remb1, and ARH77) were characterized by the absence of Gb3 at the cell surface detected by cytofluorometry or cell-surface labeling. The cell lines Priess and Remb1 did not contain Gb3 and showed a low alpha-galactosyltransferase activity for Gb3 synthesis. However, the cell line ARH77, though it did not express Gb3 at the cell surface, was found to contain a large chemical quantity of Gb3 and a high level of alpha-galactosyltransferase activity for Gb3 synthesis. However, Gb3 of ARH77 cells was exposed by sialidase treatment, but not by protease treatment, although Gb3 itself was not sialylated. The crypticity of Gb3 in ARH77 cells could be associated with an adjacent sialosyl residue of a second glycoconjugate at the cell surface, in the same way as Gg3 in mouse lymphoma L5178 (Urdal, D. L., and Hakomori, S. (1983) J. Biol. Chem. 258, 6869-6874). Thus, the expression in Burkitt and non-Burkitt lymphoma is dependent on (i) Gb3 synthesis due to alpha-galactosyltransferase activity and (ii) membrane organization of Gb3, which may be controlled through interaction with the sialosyl residue of a second glycoconjugate.
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PMID:Enzymatic and organizational difference in expression of a Burkitt lymphoma-associated antigen (globotriaosylceramide) in Burkitt lymphoma and lymphoblastoid cell lines. 643 3

Transferrin receptor (TfR) has been identified as a candidate IgA1 receptor expressed on human mesangial cells (HMC). TfR binds IgA1 but not IgA2, co-localizes with mesangial IgA1 deposits, and is overexpressed in patients with IgA nephropathy (IgAN). Here, structural requirements of IgA1 for its interaction with mesangial TfR were analyzed. Polymeric but not monomeric IgA1 interacted with TfR on cultured HMC and mediates internalization. IgA1 binding was significantly inhibited (>50%) by soluble forms of both TfR1 and TfR2, confirming that TfR serves as mesangial IgA1 receptor. Hypogalactosylated serum IgA1 from patients with IgAN bound TfR more efficiently than IgA1 from healthy individuals. Serum IgA immune complexes from patients with IgAN containing aberrantly glycosylated IgA1 bound more avidly to TfR than those from normal individuals. This binding was significantly inhibited by soluble TfR, highlighting the role of TfR in mesangial IgA1 deposition. For addressing the potential role of glycosylation sites in IgA1-TfR interaction, a variety of recombinant dimeric IgA1 molecules were used in binding studies on TfR with Daudi cells that express only TfR as IgA receptor. Deletion of either N- or O-linked glycosylation sites abrogated IgA1 binding to TfR, suggesting that sugars are essential for IgA1 binding. However, sialidase and beta-galactosidase treatment of IgA1 significantly enhanced IgA1/TfR interaction. These results indicate that aberrant glycosylation of IgA1 as well as immune complex formation constitute essential factors favoring mesangial TfR-IgA1 interaction as initial steps in IgAN pathogenesis.
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PMID:Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. 1497 64