TGF-β sensitivity is determined by N-linked glycosylation of the type II TGF-β receptor

• DOI: 10.1042/bj20111923
• Publication Date: 2012-05-11T08:18:52Z
• Authors: Young-Woong Kim; Jinah Park; Hyun-Ju Lee; So-Young Lee; Seong-Jin Kim
• Keywords: Tunicamycin; N-linked glycosylation; HEK 293 cells

N-linked glycosylation is a critical determinant of protein structure and function, regulating processes such as folding, stability localization, ligand–receptor binding intracellular signalling. TβRII [type II TGF-β (transforming growth factor β) receptor] plays crucial role in the signalling pathway. Although was first demonstrated over decade ago, it unclear how this modification influenced biology. In present study, we show that inhibiting process successfully hinders TGF-β1 to subsequently renders cells resistant The lung cancer cell line A549, gastric carcinoma MKN1 immortal HEK (human embryonic kidney)-293 exhibit reduced when either treated with two inhibitors, including tunicamycin (a potent inhibitor) kifunensine [an inhibitor ER (endoplasmic reticulum) Golgi mannosidase I family members], or introduced non-glycosylated mutant version TβRII. We demonstrate defective prevents proteins from being transported surface. Moreover, clearly not only complex type, but also high-mannose can be localized on Collectively, these findings essentially required for successful surface transportation TβRII, suggesting novel mechanism by which sensitivity regulated levels