Human N-Acetylglucosamine-6-O-Sulfotransferase Involved in the Biosynthesis of 6-Sulfo Sialyl Lewis X: Molecular Cloning, Chromosomal Mapping, and Expression in Various Organs and Tumor Cells.

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概要

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• N-Acetylglucosamine-6-O-sulfotransferase catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of a non-reducing N-acetylglucosamine (GlcNAc) residue. We have cloned human GlcNAc-6-O-sulfotransferase cDNA, based on the sequence homology to cloned cDNA of mouse GlcNAc-6-O-sulfotransferase. The predicted protein sequence of the human enzyme was highly homologous to that of the mouse enzyme; in the 363 amino acid stretch of the catalytic region, the two proteins were nearly identical except for conservative changes in 3 amino acid residues. The expressed enzyme transferred sulfate to GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAc. Co-transfection of the enzyme cDNA and fucosyltransferase VII cDNA into COS-7 cells resulted in cell surface expression of 6-sulfo sialyl Lewis X. Fluorescence in situ hybridization analysis revealed that the GlcNAc-6-O-sulfotransferase gene is located on human chromosome 7q31. mRNA of the human enzyme was strongly expressed in the bone marrow, peripheral blood leukocytes, spleen, brain, spinal cord, ovary, and placenta, and moderate levels of expression were observed in many organs including lymph nodes and thymus. In situ hybridization with the mouse system showed that the transcript was localized in specific regions of the brain, i.e. pyramidal cells in the CA3 subregion of the hippocampus, cerebellar nucleus and Purkinje cells. Among human tumor cells, strong expression of the mRNA was found in MOLT-4 and Jarkat lymphoblastic leukemia cells, Raji lymphoma cells, K-562 chronic myelogeneous leukemia cells, U251 glioma cells, and G361 melanoma cells. Carbohydrate structures synthesized by the sulfotransferase may be involved in various aspects of the differentiation and behavior of blood cells, their progenitor cells, and neurons in the central nervous system.

• 社団法人 日本生化学会の論文

著者

• Kannagi Reiji

  Program Of Experimental Pathology Aichi Cancer Center Research Institute

• Kadomatsu Kenji

  Department Of Biochemistry Nagoya University Graduate School Of Medicine

• OGAWA Haruko

  Surgery II Nagoya Univesity School of Medicine

• YAMAKAWA Taishi

  Departments of Biochemistry Nagoya Univesity School of Medicine

• MITSUOKA Chikako

  Program of Experimental Pathology, Aichi Cancer Center, Research Institute

• YOKOYAMA Itsuo

  Surgery II Nagoya Univesity School of Medicine

• OZAKI Toshinori

  Division of Biochemistry, Chiba Cancer Center Research Institute

• KANAME Tadashi

  Department of Biochemistry, Nagoya University School of Medicine

• Yamamura Ken-ichi

  Department Of Developmental Genetics Institute Of Molecular Embryology And Genetics

• Habuchi Osami

  Department Of Chemistry Aichi University Of Education

• Uchimura Kenji

  Department Of Anatomy University Of California

• Ozaki Toshinori

  Division Of Biochemistry Chiba Cancer Center Research Institute

• Muramatsu Hideki

  Department Of Internal Medicine And Molecular Science Nagoya City University Graduate School Of Medi

• Nakagawara Akira

  Division Of Biochemistry And Innovative Cancer Therapeutics Chiba Cancer Center Research Institute

• Fan Qi-Wen

  Department of Biochemistry, Nagoya University School of Medicine

• MURAMATSU Takashi

  Department of Animal Breeding and Reproduction, Faculty of Agriculture Utsunomiya University

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