Differentiation elicits negative regulation of human β‐galactoside α2,6‐sialyltransferase at the mRNA level in the HL‐60 cell line

Taniguchi, Akiyoshi; Higai, Koji; Hasegawa, Yūko; Utsumi, K; Matsumoto, Kojiro

doi:10.1016/s0014-5793(98)01548-8

Cited by 26 publications

(11 citation statements)

References 40 publications

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“…In our study, two myeloid cell lines that normally undergo differentiation in response to PMA (U937 and THP-1 cells) were shown to have decreased levels of ST6Gal I following PMA treatment. Consistent with these results, PMA has been previously shown to down-regulate ST6Gal I in HL-60 myeloid cells (27). Unlike U937 and THP-1 cells, myeloid cells that have been selected for PMA resistance (PRU cells) do not down-regulate ST6Gal I in response to PMA, do not express hyposialylated ␤ 1 integrins, and, finally, do not bind to fibronectin following PMA treatment.…”

Section: Discussionsupporting

confidence: 74%

“…Expression of the ST6Gal I sialyltransferase is known to be developmentally regulated (25,26), and the levels of this enzyme vary in response to cell differentiation status (27)(28)(29). In our study, two myeloid cell lines that normally undergo differentiation in response to PMA (U937 and THP-1 cells) were shown to have decreased levels of ST6Gal I following PMA treatment.…”

Section: Discussionmentioning

confidence: 51%

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Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Semel

Seales

Singhal

et al. 2002

Journal of Biological Chemistry

101

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Despite numerous reports suggesting that ␤ 1 integrin receptors undergo differential glycosylation, the potential role of N-linked carbohydrates in modulating integrin function has been largely ignored. In the present study, we find that ␤ 1 integrins are differentially glycosylated during phorbol ester (PMA)-stimulated differentiation of myeloid cells along the monocyte/macrophage lineage. PMA treatment of two myeloid cell lines, U937 and THP-1, induces a down-regulation in expression of the ST6Gal I sialyltransferase. Correspondingly, the ␤ 1 integrin subunit becomes hyposialylated, suggesting that the ␤ 1 integrin is a substrate for this enzyme. The expression of hyposialylated ␤ 1 integrin isoforms is temporally correlated with enhanced binding of myeloid cells to fibronectin, and, importantly, fibronectin binding is inhibited when the Golgi disrupter, brefeldin A, is used to block the expression of the hyposialylated form. Consistent with the observation that cells with hyposialylated integrins are more adhesive to fibronectin, we demonstrate that the enzymatic removal of sialic acid residues from purified ␣ 5 ␤ 1 integrins stimulates fibronectin binding by these integrins. These data support the hypothesis that unsialylated ␤ 1 integrins are more adhesive to fibronectin, although desialylation of ␣ 5 subunits could also contribute to increased fibronectin binding. Collectively our results suggest a novel mechanism for regulation of the ␤ 1 integrin family of cell adhesion receptors.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 51%

Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Semel

Seales

Singhal

et al. 2002

Journal of Biological Chemistry

101

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“…A moderate increase of ST6GAL1 gene expression was also detected on PMA-differentiated THP-1 cells, whereas this enzyme was down-regulated in HL-60 50 . Our result is in accordance with a recent study that documented an increased expression of ST6GAL1 protein after differentiation of THP-1, as established by western-blot analysis.…”

Section: Discussionmentioning

confidence: 87%

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

et al. 2016

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The human acute monocytic leukemia cell line THP-1 is widely used as an in vitro phagocytic cell model because it exhibits several immune properties similar to native monocyte-derived macrophages. In this study, we investigated the alteration of N- and O-linked glycans as well as glycosphingolipids, during THP-1 differentiation, combining mass spectrometry, flow cytometry, and quantitative real-time PCR. Mass spectrometry revealed that macrophage differentiation led to a marked upregulation of expression of GM3 ganglioside as well as an increase in complex-type structures, particularly triantennary glycans, occurring at the expense of high-mannose N-glycans. Moreover, we observed a slight decrease in the proportion of multifucosylated N-glycans and α2,6-sialylation. The uncovered changes in glycosylation correlated with variations of gene expression of relevant glycosyltransferases and glycosidases including sialyltransferases, β-N-acetylglucosaminyltransferases, fucosyltransferases, and neuraminidase. Furthermore, using flow cytometry and antibodies directed against glycan structures, we confirmed that the alteration of glycosylation occurs at the cell surface of THP-1 macrophage-like cells. Altogether, we established that macrophagic maturation of THP-1 induces dramatic modifications of the surface glycosylation pattern that may result in differential interaction of monocytic and macrophagic THP-1 with immune or bacterial lectins.

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“…Glycan profiling studies reveal that ␣2,6-sialylated structures comprise the predominant type of complex N-glycans in freshly isolated CD4 and CD8 T cells, whereas activated T cells exhibit a dramatic decrease in ␣2,6-sialylated glycans due to down-regulated expression of ST6Gal-I (35,36). ST6Gal-I expression and activity are similarly down-regulated during dendritic cell maturation (37,38) and differentiation of primary monocytes and promonocytic cell lines along the macrophage lineage (27,30,39). Collectively, these results hint that decreased ␣2,6-sialylation may be necessary for some aspect of immune cell maturation or activation.…”

Section: Role Of St6gal-i-mediated ␣26-sialylation In Regulating Galmentioning

confidence: 99%

Emerging Role of α2,6-Sialic Acid as a Negative Regulator of Galectin Binding and Function

Zhuo

Bellis

2011

Journal of Biological Chemistry

152

122

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Galectins are ␤-galactoside-binding lectins that regulate diverse cell behaviors, including adhesion, migration, proliferation, and apoptosis. Galectins can be expressed both intracellularly and extracellularly, and extracellular galectins mediate their effects by associating with cell-surface oligosaccharides. Despite intensive current interest in galectins, strikingly few studies have focused on a key enzyme that acts to inhibit galectin signaling, namely ␤-galactoside ␣2,6-sialyltransferase (ST6Gal-I). ST6Gal-I adds an ␣2,6-linked sialic acid to the terminal galactose of N-linked glycans, and this modification blocks galectin binding to ␤-galactosides. This minireview summarizes the evidence suggesting that ST6Gal-I activity serves as an "off switch" for galectin function.Sialic acids comprise a family of nine-carbon sugars added to the termini of oligosaccharides found on secreted or cellsurface glycoproteins and glycolipids (1). Because of their negative charge and relatively large size, sialic acids can mask important functional domains on surface glycoproteins and also serve more generally to protect the cell from various types of assault (2). However, evidence is emerging that sialic acids mediate specific cellular and molecular recognition by regulating association with glycan-binding proteins such as lectins. For example, sialic acids bind specifically to the siglec 2 family of lectins (3), whereas other types of glycan/lectin interactions are conversely inhibited by sialylation. Thus, sialic acids are positioned to play a pivotal role in regulating lectindependent cell/cell and cell/matrix interactions. Sialic acids are added to glycans via ␣2,3-, ␣2,6-, or ␣2,8-linkages, and these linkages are directed by distinct sialyltransferases. ␤-Galactoside ␣2,6-sialyltransferase (ST6Gal-I) is one of the principal enzymes responsible for the addition of ␣2,6-linked sialic acids to the Gal␤1,4GlcNAc disaccharide (4), which is found mainly on N-glycans and, to a lesser extent, on O-glycans. In this minireview, we summarize the evidence suggesting that ST6Gal-I-mediated ␣2,6-sialylation inhibits binding of N-glycans to galectin-type lectins, thereby serving as a negative regulator of galectin-dependent cell responses (of note, ␣2,6-sialic acid/siglec interactions, although of equal biologic importance, will be not be discussed herein due to the availability of other reviews on this topic (3, 5)). GalectinsGalectins are animal lectins that bind ␤-galactosides through their conserved carbohydrate recognition domains (CRDs) (6, 7). At least 15 mammalian galectins have been identified, and these are subdivided into three different groups based on their biochemical structure (Fig. 1). The prototype group (galectin (Gal)-1, -2, -5, -7, -10, -11, -13, -14, and -15) contains one CRD and a short N-terminal sequence. Members of this group typically assemble into noncovalent homodimers. The chimeric group, of which Gal-3 is the only member, contains one CRD and an extended N-terminal domain with a repeated collagen-like seq...

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Differentiation elicits negative regulation of human β‐galactoside α2,6‐sialyltransferase at the mRNA level in the HL‐60 cell line

Cited by 26 publications

References 40 publications

Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

Emerging Role of α2,6-Sialic Acid as a Negative Regulator of Galectin Binding and Function

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