Sulfation of N-Acetylglucosamine by Chondroitin 6-Sulfotransferase 2 (GST-5)

Bhakta, Sunil; Bartes, Alexander; Bowman, Kendra G.; Kao, Wei-Ming; Polsky, Irene; Lee, Jin Kyu; Cook, Brian N.; Bruehl, Richard E.; Rosen, Steven D.; Bertozzi, Carolyn R.; Hemmerich, Stefan

doi:10.1074/jbc.m006414200

Cited by 39 publications

(26 citation statements)

References 42 publications

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“…Among the family members, the closest relative to GlcNAc6ST-1 with respect to the stem region is GlcNAc6ST-4 (52,53). This enzyme has an extended stem of similar size, as well as two Cys residues in similar locations.…”

Section: Discussionmentioning

confidence: 99%

The Stem Region of the Sulfotransferase GlcNAc6ST-1 Is a Determinant of Substrate Specificity

Graffenried¹,

Bertozzi

2004

Journal of Biological Chemistry

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The GlcNAc-6-sulfotransferases are a family of Golgiresident enzymes that modulate glycan function. Two members of this family, GlcNAc6ST-1 and -2, collaborate in the biosynthesis of ligands for the leukocyte adhesion molecule L-selectin. Although their biochemical properties are similar in vitro, the enzymes have distinct glycoprotein substrate preferences in vivo. The sulfotransferases share similar overall architecture with the exception of an extended stem region in GlcNAc6ST-1 that is absent in GlcNAc6ST-2. In this study we probed the importance of the stem region with respect to substrate preference, localization, and oligomerization. Analysis of truncation mutants demonstrated that perturbation of the stem region of GlcNAc6ST-1 affects the cellular substrate preference of the enzyme without altering its retention within the Golgi. A chimeric enzyme comprising the stem region of GlcNAc6ST-1 inserted between the catalytic and transmembrane domains of GlcNAc6ST-2 had the same substrate preference as native GlcNAc6ST-1. In cells, GlcNAc6ST-1 exists as a dimer; two cysteine residues within the stem and transmembrane domain were found to be critical for dimerization. However, disruption of the dimer by mutagenesis did not affect either localization or substrate preference. Collectively, these results indicate that the stem region of GlcNAc6ST-1 influences substrate specificity, independent of its role in dimerization or Golgi retention.

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Section: Discussionmentioning

confidence: 99%

The Stem Region of the Sulfotransferase GlcNAc6ST-1 Is a Determinant of Substrate Specificity

Graffenried¹,

Bertozzi

2004

Journal of Biological Chemistry

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“…56) In vivo GST-5 function of GlcNAc6ST-4 is unknown. mice than in the GlcNAc6ST-1-deficient mice (Fig.…”

Section: )mentioning

confidence: 99%

Roles of Sulfated Glycans in Lymphocyte Homing

Kawashima

2006

Biological & Pharmaceutical Bulletin

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LYMPHOCYTE HOMINGLymphocytes are generated in primary lymphoid organs, such as the bone marrow and thymus, and migrate to the lymph nodes, Peyer's patches, and spleen, known as secondary lymphoid organs, where the immune responses occur. Lymphocytes that migrate to the lymph nodes and Peyer's patches emigrate through the efferent lymph, unless they encounter their cognate antigens. Lymphocytes that emigrate through the lymph return to the bloodstream through the thoracic duct, through which lymph fluid drains into the blood. Lymphocytes that return to the blood migrate again into the secondary lymphoid organs. This circulatory process is called lymphocyte recirculation or lymphocyte homing. Antigens that enter the body from peripheral tissues such as the skin accumulate in the lymph nodes. Antigens in the blood are collected in the spleen. Those in food are taken up by M cells residing in the mucosal intestinal epithelial barrier and accumulate in the Peyer's patches. Thus, the secondary lymphoid organs are the sites where foreign antigens accumulate and immune responses primarily occur. The homing of lymphocytes into secondary lymphoid organs through the blood and lymph circulation raises the likelihood that lymphocytes will encounter antigens. In other words, lymphocyte homing is important for the immune system to recognize foreign antigens efficiently.Lymphocytes migrate into the parenchyma of lymph nodes through specialized blood vessels called high endothelial venules (HEV). HEV have a characteristic cuboidal morphology and a prominent Golgi complex where unique sulfated glycans are synthesized, as discussed later. Lymphocyte migration is achieved by a series of interactions between lymphocytes and HEV 1) ( Fig. 1): (i) the rolling of lymphocytes, which is mediated by L-selectin on the lymphocytes and sulfated glycans on the HEV; (ii) activation of the lymphocytes by chemokines presented on the surface of the HEV by heparan sulfate, a glycosaminoglycan; (iii) firm attachment of the lymphocytes through the interaction between b2 integrins on the lymphocytes and intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1) on the HEV; and (iv) transmigration. HOMING RECEPTOR L-SELECTINThe homing receptor L-selectin (LECAM-1, CD62L, LAM-1) was first identified as an antigen recognized by the monoclonal antibody (mAb) MEL-14, which blocks the binding of lymphocytes to HEV in vitro and in vivo. L-selectin is an adhesion molecule that recognizes carbohydrates through a lectin-like domain in its N-terminus, through which it mediates the initial tethering and rolling of lymphocytes on the surface of HEV. L-selectin is localized to the tips of microvilli, 2) which is advantageous for the initial tethering to HEV-borne carbohydrate ligands. To date, several kinds of glycoprotein ligands for L-selectin have been identified (see below).L-selectin is expressed not only on lymphocytes, but also on other types of leukocytes, such as neutrophils and monocytes. L-selectin is involved in the infilt...

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“…A mouse IGlcNAc6ST has combined activities of the two enzymes, GlcNAc6ST-3 and -5, and can synthesize KS, as well as 6-SO 4 -GlcNAc linkages in glycoproteins [79,80]. GlcNAc6ST-4 is expressed in many different organs and can utilize N-acetyl-lactosamine chains as substrates [81,82].…”

Section: Glcnac6stsmentioning

confidence: 99%

Sulphotransferases acting on mucin-type oligosaccharides

Brockhausen

2003

Biochemical Society Transactions

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This review summarizes the occurrence, properties and role in mucin O-glycosylation pathways of the various members of glycoprotein sulphotransferase families. Although a number of sulphotransferases have been cloned that act on mucin-type substrates in vitro, it is still difficult to determine exactly which enzymes are responsible for mucin sulphation in vivo. Sulphotransferases play a critical role in determining the chemical, physical and biological properties of mucins. Several of these enzymes have been shown to differ in expression and activity in cancer and inflammation.

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Sulfation of N-Acetylglucosamine by Chondroitin 6-Sulfotransferase 2 (GST-5)

Cited by 39 publications

References 42 publications

The Stem Region of the Sulfotransferase GlcNAc6ST-1 Is a Determinant of Substrate Specificity

The Stem Region of the Sulfotransferase GlcNAc6ST-1 Is a Determinant of Substrate Specificity

Roles of Sulfated Glycans in Lymphocyte Homing

Sulphotransferases acting on mucin-type oligosaccharides

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