N-glycan of ErbB family plays a crucial role in dimer formation and tumor promotion

Takahashi, M.; Yokoe, Shunichi; Asahi, Michio; Lee, Seung Ho; Li, Wei; Osumi, Daisuke; Miyoshi, Eiji; Taniguchi, Naoyuki

doi:10.1016/j.bbagen.2007.10.019

Cited by 55 publications

(58 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1 D-F Sialylation of EGFR in CL1 Cells. Among these CL1-5 uniquely expressed sialyl proteins (Table S1), EGFR was chosen for further investigation for its important role in promoting tumor growth and metastasis, and the link of EGFR N-linked glycosylation to its function (14,16,17). To verify if EGFR in CL1-5 was oversialylated, we next examined the expression and sialylation of EGFR in CL1-0 and CL1-5 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The major glycoforms of EGFR in an epidermoid carcinoma cell line, A431, have been identified (13). Some previous studies have indicated that the glycans could participate in regulating certain functions of EGFR (14). For example, mutagenesis to remove the Asn 420 and 579-linked glycans of EGFR and Asn 418-linked glycans of ErbB3 causes ligand-independent spontaneous dimerization (15)(16)(17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells

Liu

Yen

Chen

et al. 2011

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

358

317

View full text Add to dashboard Cite

Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal glycosylation in tumor cells affects cancer progression and malignancy. In the current study, we have identified sialylated proteins using an alkynyl sugar probe in two different lung cancer cell lines, CL1-0 and CL1-5 with distinct invasiveness derived from the same parental cell line. Among the identified sialylated proteins, epidermal growth factor receptor (EGFR) was chosen to understand the effect of sialylation on its function. We have determined the differences in glycan sequences of EGFR in both cells and observed higher sialylation and fucosylation of EGFR in CL1-5 than in CL1-0. Further study suggested that overexpression of sialyltransferases in CL1-5 and α1,3-fucosyltransferases (FUT4 or FUT6) in CL1-5 and A549 cells would suppress EGFR dimerization and phosphorylation upon EGF treatment, as compared to the control and CL1-0 cells. Such modulating effects on EGFR dimerization were further confirmed by sialidase or fucosidase treatment. Thus, increasing sialylation and fucosylation could attenuate EGFRmediated invasion of lung cancer cells. However, incorporation of the core fucose by α1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.sialic acid | glycoproteomics | glycan sequencing | click chemistry | mass spectrometry

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells

Liu

Yen

Chen

et al. 2011

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

358

317

View full text Add to dashboard Cite

show abstract

“…We also demonstrated that N-glycan on Asn-418 of ErbB3 is involved in ligand-induced ErbB2-ErbB3 heterodimer formation and downstream signaling (23). It is possible that N-glycan in domain III of ErbB is involved in the structural maintenance of extracellular domains (24).…”

mentioning

confidence: 86%

Suppression of Heregulin β Signaling by the Single N-Glycan Deletion Mutant of Soluble ErbB3 Protein

Takahashi

Hasegawa

Ikeda

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Extracellular domain of ErbBs (sErbBs) down-regulates growth factor signaling. Results: sErbB3 acts on ErbB3-containing heterodimers to suppress heregulin signaling, and the effects are enhanced by single N-glycan deletion. Conclusion: N-Glycan on Asn-418 controls the ability of sErbB3 to suppress heregulin signaling. Significance: Provides new insights toward understanding the mechanisms by which N-glycan regulates ErbB receptors.

show abstract

“…The issue of whether the conformations of spontaneously dimerized EGFR-N420Q (14) and ErbB3-N418Q are similar to those produced by ligand-induced dimerization is not known at present; however, the oligosaccharide on the Asn 420 of EGFR or the Asn 418 of ErbB3 might be involved in tethering. Consequently, deleting these oligosaccharides would result in spontaneous dimerization (22,23). It is assumed that some N-glycans might act to prevent unnecessary protein-protein interactions.…”

Section: E Discussionmentioning

confidence: 99%

The role of ErbB3 N-glycan in dimer formation: Implications for transforming activity

Yokoe

2008

TIGG

Self Cite

View full text Add to dashboard Cite

The ErbB2/ErbB3 heterodimer elicits potent mitogenic and transforming signals, and clinical studies indicate that these receptors play an important role in tumor incidence and progression. In this study, a series of human ErbB3 mutants devoid of N-glycans expressed in Flp-In-CHO cells were used to determine whether N-glycosylation is involved in the function of ErbB3. A crosslinking study showed that the Asn 418 to Gln mutant (N418Q) of ErbB3 underwent heregulin (HRG)-independent autodimerization. Furthermore, ErbB3-N418Q autodimerized with ErbB2 in the absence of HRG, and receptor tyrosine phosphorylation and subsequent extracellular signalregulated kinase (ERK) and Akt phosphorylation were promoted. A cell proliferation assay and a soft agar colony formation assay demonstrated that ErbB2/ErbB3-N418Q co-expression promoted cell proliferation and colony formation in soft agar in ERK-and Akt-dependent manners. ErbB2/ErbB3-N418Q co-expression also promoted the growth of tumors in athymic nude mice when injected subcutaneously. These results suggest that the Asn 418 -linked N-glycan in ErbB3 plays a crucial role in regulating receptor dimer formation and transforming activity.

show abstract

N-glycan of ErbB family plays a crucial role in dimer formation and tumor promotion

Cited by 55 publications

References 28 publications

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells

Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells

Suppression of Heregulin β Signaling by the Single N-Glycan Deletion Mutant of Soluble ErbB3 Protein

The role of ErbB3 N-glycan in dimer formation: Implications for transforming activity

Contact Info

Product

Resources

About