The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.

Zhou, Qun; Moore, Kevin L.; Smith, David F.; Varki, Ajit; McEver, Rodger P.; Cummings, Richard D.

doi:10.1083/jcb.115.2.557

Cited by 172 publications

(54 citation statements)

References 62 publications

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“…C2GnT and an ␣1-3 Fucosyltransferase-We next used a cell adhesion assay to measure the modifications required for PSGL-1 expressed on CHO cells to bind P-and E-selectin. CHO cells transfected with an ␣1-3 fucosyltransferase express sLe x on the cell surface, and adhere to immobilized P-or E-selectin under certain experimental conditions (23,25,38). To measure PSGL-1-dependent adhesion, we developed conditions in which CHO cells expressing an ␣1-3 fucosyltransferase did not adhere to P-or E-selectin.…”

Section: Fluid-phase P-selectin Does Not Bind Psgl-1 Co-expressed Witmentioning

confidence: 99%

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Post-translational Modifications of Recombinant P-selectin Glycoprotein Ligand-1 Required for Binding to P- and E-selectin

Li¹,

Wilkins

Crawley

et al. 1996

Journal of Biological Chemistry

318

259

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P-selectin glycoprotein ligand-1 (PSGL-1) is a mucinlike ligand for P-and E-selectin on human leukocytes. PSGL-1 requires sialylated, fucosylated O-linked glycans and tyrosine sulfate to bind P-selectin. Less is known about the determinants that PSGL-1 requires to bind E-selectin. To further define the modifications required for PSGL-1 to bind P-and E-selectin, we transfected Chinese hamster ovary (CHO) cells with cDNAs for PSGL-1 and specific glycosyltransferases. CHO cells synthesize only core 1 O-linked glycans (Gal␤1-3Gal-NAc␣1-Ser/Thr); they lack core 2 O-linked glycans (Gal␤1-3(Gal␤1-4GlcNAc␤1-6)GalNAc␣1-Ser/Thr) because they do not express the core 2 ␤1-6-N-acetylglucosaminyltransferase (C2GnT). CHO cells also lack ␣1-3 fucosyltransferase activity. PSGL-1 expressed on transfected CHO cells bound P-and E-selectin only when it was co-expressed with both C2GnT and an ␣1-3 fucosyltransferase (Fuc-TIII, Fuc-TIV, or Fuc-TVII). Chromatography of ␤-eliminated O-linked glycans from PSGL-1 co-expressed with C2GnT confirmed synthesis of core 2 structures. Tyrosine residues on PSGL-1 expressed in CHO cells were shown to be sulfated. Phenylalanine replacement of three tyrosines within a consensus sequence for tyrosine sulfation abolished binding to Pselectin but not to E-selectin. These results demonstrate that PSGL-1 requires core 2 O-linked glycans that are sialylated and fucosylated to bind P-and E-selectin. PSGL-1 also requires tyrosine sulfate to bind P-selectin but not E-selectin.

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Section: Fluid-phase P-selectin Does Not Bind Psgl-1 Co-expressed Witmentioning

confidence: 99%

“…Formation of the core 2 structure is catalyzed by C2GnT (21). CHO cells have no endogeneous ␣1-3 fucosyltransferase or C2GnT activity (35,37,38).…”

Section: Psgl-1 Expressed On Cho Cells Binds Fluid-phase P-selectin Omentioning

confidence: 99%

Post-translational Modifications of Recombinant P-selectin Glycoprotein Ligand-1 Required for Binding to P- and E-selectin

Li¹,

Wilkins

Crawley

et al. 1996

Journal of Biological Chemistry

318

259

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“…On endothelial surfaces, P-selectin supports leucocyte rolling by shear-resistant, Ca 2þ -dependent interactions with its ligands on the leucocyte surface (Geng et al, 1990(Geng et al, , 1991Zhou et al, 1991;Lawrence & Springer, 1991). The role of P-selectin is thought to be important, especially in the earlier phase of inflammation, because surface expression of P-selectin is rapidly induced via translocation of the molecule, whereas de novo synthesis of E-selectin (Bevilacqua et al, 1987) and one of the ligands of L-selectin (Spertini et al, 1991) is reportedly induced by cytokine activation.…”

mentioning

confidence: 99%

Re‐expression of functional P‐selectin molecules on the endothelial cell surface by repeated stimulation with thrombin

et al. 1997

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Summary. P-selectin (GMP-140, PADGEM, CD62P) is a cell adhesion receptor which is believed to play an important role in inflammatory diseases by supporting leucocyte rolling. P-selectin is located on the granule membrane of WeibelPalade bodies in resting endothelial cells and is expressed on the cell surface during cellular activation with various stimulators such as thrombin. Thereafter, P-selectin is internalized and sorted to the Golgi region and Weibel-Palade bodies again. However, whether P-selectin is re-expressed upon subsequent cellular stimulation has, to date, been unclear.To address this question, we measured the cellular content and surface expression of P-selectin, using indirect immunofluorescence and confocal laser cytometry. Surface expression of P-selectin reached a maximum < 2 min after thrombin stimulation and declined to basal levels after 180 min. Rechallenge with thrombin induced rapid surface re-expression of P-selectin, which was independent of de novo protein synthesis, since cycloheximide did not inhibit re-expression. Moreover, re-expressed P-selectin supported the adherence of HL60 promyelocytic cells.These results clearly demonstrated that functional P-selectin molecule was recycled after repeated stimulation with thrombin, raising the possibility that P-selectin is involved in chronic inflammation.

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“…E-selectin recognizes sialyl Lewis X (SLeX) on the surface of neutrophils (29)(30)(31). P-selectin also binds SLeX on neutrophils or leukocytes with a lower affinity (32,33). L-selectin weakly recognizes SLex on endothelial cells, but the affinity is higher with a sulfate group on the six position of Gal (34,35) or, perhaps more likely, on the six position of the GlcNAc residue (33,36).…”

Section: Selectins and Their Carbohydrate Ligands In Cell Adhesionmentioning

confidence: 99%

Intervention of carbohydrate recognition by proteins and nucleic acids.

Sears

Wong

1996

Proc. Natl. Acad. Sci. U.S.A.

113

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Carbohydrates in biological systems are often associated with specific recognition and signaling processes leading to important biological functions and diseases. Considerable efforts have been directed toward understanding and mimicking the recognition processes and developing effective agents to control the processes. The pace of discovery research in glycobiology and development of carbohydratebased therapeutics, however, has been relatively slow due to the lack of appropriate strategies and methods available for carbohydrate-related research. This review summarizes some of the most recent developments in the field, with particular emphasis on work from our laboratories regarding the use of chemoenzymatic strategies to tackle the carbohydrate recognition problem. Highlights include the study of selectincarbohydrate and aminoglycoside-RNA interactions and development of agents for the intervention of these recognition processes.Of the three major classes of biomolecules, carbohydrates perhaps are the least exploited. It has been known that carbohydrates can serve as structural components of natural products, as energy sources, or, more interestingly, as key elements in various molecular recognition processes, including bacterial and viral infections, cell adhesion in inflammation and metastasis, differentiation, development, regulation, and many other intercellular communication and signal transduction events (1). [Representative structures are presented in Fig. 1 (2-16).] The precise mechanism of many carbohydratemediated recognition processes are, however, not well understood, and, though potential opportunities exist, the pace of development of carbohydrate-based pharmaceuticals has been slower than that of the other classes of biomolecules. Several reasons may be attributed to this slow pace of development. First, some technical problems in the field are impossible or difficult to solve. There is no PCR equivalent replication system available for the amplification of minute amounts of carbohydrates to facilitate structure analysis and synthesis, and there is no machine available for the solid-phase synthesis of oligosaccharides to facilitate the study of their functions. In addition, synthesis of oligosaccharides in large quantities for therapeutic evaluation and development is in general very difficult and expensive. Second, carbohydrates generally possess undesirable properties for drug development. The affinity of carbohydrates for their protein receptors is relatively weak (17-21), with dissociation constants in the millimolar range, and carbohydrates are generally orally inactive and sensitive to enzymes in vivo. As a result, carbohydrates may only be used as injectable form for the treatment of acute symptoms.Understanding carbohydrate recognition is important, however, as this recognition process often occurs at the early stage of disease development, and intervention of such process may be beneficial. Furthermore, understanding the mechanism of carbohydrate recognition may lead to the devel...

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The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.

Cited by 172 publications

References 62 publications

Post-translational Modifications of Recombinant P-selectin Glycoprotein Ligand-1 Required for Binding to P- and E-selectin

Post-translational Modifications of Recombinant P-selectin Glycoprotein Ligand-1 Required for Binding to P- and E-selectin

Re‐expression of functional P‐selectin molecules on the endothelial cell surface by repeated stimulation with thrombin

Intervention of carbohydrate recognition by proteins and nucleic acids.

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