N-acetylglucosaminyltransferase V modifies the signaling pathway of epidermal growth factor receptor |
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Authors: | P?Guo Q?Y?Wang H?B?Guo Z?H?Shen Email author" target="_blank">H?L?ChenEmail author |
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Institution: | (1) Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical College, Fudan University, 200032 Shanghai, China |
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Abstract: | Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human H7721 hepatocarcinoma cells
resulted in an increase in the N-acetylglucosamine 1,6mannose 1,3- branch (GnT-V product) on the
N-glycans of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF binding and tyrosine
autophosphorylation, but showed little effect on the expression of EGFR protein. The phosphorylation at T308,
S473 and tyrosine residue(s) and the activity of protein kinase B (Akt/PKB) as well as the phosphorylation of
p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) before and after EGF stimulation were
concomitantly increased. Conversely, in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results
were the reverse of those with GnTV-S-transfected cells. After the cells were treated with 1-deoxymannojirimycin,
an inhibitor of N-glycan processing at high mannose, or antibody against the extracellular glycan domain of EGFR,
the differences in PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and mock-transfected
cells were significantly attenuated. These findings indicate that the altered expression of GnT-V will change the
glycan structure and function of EGFR, which may modify downstream signal transduction.Received 24 March 2004; received after revision 1 May 2004; accepted 25 May 2004 |
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Keywords: | Receptor of epidermal growth factor N-acetylglucosaminyltransferase V phosphorylation Akt/PKB MEK p44/42 MAPK |
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