Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes.

Marathe DD; Chandrasekaran EV; Lau JTMatta KLNeelamegham S

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Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes.

机译：Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes.

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The application of systems biology methods in the emerging field of glycomics requires the collection and integration of glycosyltransferase data at the gene and enzyme level for the purpose of hypothesis generation. We systematically examined the relationship between gene expression, glycosyltransferase activity, glycan expression, and selectin-binding function in different systems, including human neutrophils, undifferentiated HL-60 (human promyelocytic cells), differentiated HL-60, and HL-60 synchronized in specific growth phases. Results demonstrate that 1) the sLe(X) (sialyl-Lewis-X) epitope is expressed in P-selectin glycoprotein ligand-1 (PSGL-1) from neutrophils at higher levels compared with HL-60. This variation may be due to differences in the relative activities of alpha1,3-fucosyltransferases and alpha2,3-sialyltransferases in these two cell types. 2) HL-60 cell differentiation along granulocyte lineage increased the activity of beta1,4GalT and beta1,3GlcNAcT by 1.6- to 3.2-fold. This may contribute to LacNAc chain extension as evidenced by the 1.7-fold increase in DSA-lectin (lectin recognizing LacNAc) binding to cells after differentiation. 3) The activity of enzymes contributing to sLe(X) formation in leukocytes likely varies as ST3Galbeta1,4GlcNAc < or = alpha1,3FTsialyl-LacNAc < beta1,3GlcNAcT. 4) O-glycan specific glycosyltransferase activity does not undergo periodic variation with cell cycle phases. Overall, gene expression and enzyme activity data combined with knowledge of biochemistry can predict the resulting glycan structures and yield viable experimentally testable hypothesis.

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《The FASEB Journal》 |2008年第12期|4154-4167|共14页
作者
Marathe DD; Chandrasekaran EV; Lau JTMatta KLNeelamegham S;
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作者单位

Chemical and Biological Engineering State University of New York at Buffalo, Buffalo, NY 14260, USA.;

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原文格式 PDF
正文语种英语
中图分类生物化学;
关键词
Glycosyltransferases; binding; Human; Gene Expression; 糖基转移酶类; 基因表达;

Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes.

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