Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells. 2007

Milan Raska, and Zina Moldoveanu, and Hitoshi Suzuki, and Rhubell Brown, and Rose Kulhavy, and Judit Andrasi, and Stacy Hall, and Huong L Vu, and Fredric Carlsson, and Gunnar Lindahl, and Milan Tomana, and Bruce A Julian, and Robert J Wyatt, and Jiri Mestecky, and Jan Novak
University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.

UI MeSH Term Description Entries
D007070 Immunoglobulin A Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions. IgA,IgA Antibody,IgA1,IgA2,Antibody, IgA
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000094802 beta-D-Galactoside alpha 2-6-Sialyltransferase Sialyltransferases that catalyze the transfer of N-ACETYLNEURAMINIC ACID from CYTIDINE MONOPHOSPHATE N-ACETYLNEURAMINIC ACID to the 6-OH of the GALACTOSE residue of N-GLYCANS. CMP-Acetylneuraminate Galactoside (alpha 2-6)-Sialyltransferase,CMP-N-Acetylneuraminate-Galactosylglycoprotein Sialyltransferase ST6GAL,CMP-N-Acetylneuraminate-beta-Galactoside alpha-2,6-Sialyltransferase,CMP-N-Acetylneuraminic Acid-Lactose Sialytransferase,CMP-NeuAc-Galactoside (alpha 2-6)-Sialyltransferase,CMP-Sialic Acid-N-Acetyllactosaminide alpha (2-6)-Sialyltransferase,Gal-1-4-GlcNAc alpha(2-6)-Sialyltransferase,alpha 2-6-Sialyltransferase,alpha2,6(N) Sialyltransferase,alpha6-Sialyltransferase,beta-D-Galactoside alpha-2-6-Sialyltransferase,beta-Galactoside alpha2,6-Sialyltransferase,beta-Galactosyl(1-4)N-Acetylglucosaminide alpha(2-6)-Sialyltransferase,Gal-GlcNAc(2-6)-sialyltransferase,SIAT-1,ST6(N),ST6Gal I,ST6Gal-1,2-6-Sialyltransferase, alpha,2-6-Sialyltransferase, beta-D-Galactoside alpha,Acid-Lactose Sialytransferase, CMP-N-Acetylneuraminic,CMP N Acetylneuraminate Galactosylglycoprotein Sialyltransferase ST6GAL,CMP N Acetylneuraminate beta Galactoside alpha 2,6 Sialyltransferase,CMP N Acetylneuraminic Acid Lactose Sialytransferase,SIAT 1,ST6GAL, CMP-N-Acetylneuraminate-Galactosylglycoprotein Sialyltransferase,ST6Gal 1,Sialyltransferase ST6GAL, CMP-N-Acetylneuraminate-Galactosylglycoprotein,Sialytransferase, CMP-N-Acetylneuraminic Acid-Lactose,alpha 2 6 Sialyltransferase,alpha 2-6-Sialyltransferase, beta-D-Galactoside,alpha-2,6-Sialyltransferase, CMP-N-Acetylneuraminate-beta-Galactoside,alpha-2-6-Sialyltransferase, beta-D-Galactoside,alpha2,6-Sialyltransferase, beta-Galactoside,alpha6 Sialyltransferase,beta D Galactoside alpha 2 6 Sialyltransferase,beta Galactoside alpha2,6 Sialyltransferase
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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