TGF-beta sensitivity is determined by N-linked glycosylation of the type II TGF-beta receptor
- Authors
- Kim, Young-Woong; Park, Jinah; Lee, Hyun-Ju; Lee, So-Young; Kim, Seong-Jin
- Issue Date
- 1-Aug-2012
- Publisher
- PORTLAND PRESS LTD
- Keywords
- cell surface transport; N-linked glycosylation; transforming growth factor beta sensitivity (TGF-beta sensitivity); transforming growth factor beta signalling (TGF-beta signalling); type II transforming growth factor beta receptor (T beta RII)
- Citation
- BIOCHEMICAL JOURNAL, v.445, pp.403 - 411
- Journal Title
- BIOCHEMICAL JOURNAL
- Volume
- 445
- Start Page
- 403
- End Page
- 411
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16233
- DOI
- 10.1042/BJ20111923
- ISSN
- 0264-6021
- Abstract
- N-linked 21ycosylation is a critical determinant of protein structure and function, regulating processes such as protein folding, stability and localization, ligand receptor binding and intracellular signalling. T beta RII [type II TGF-beta (transforming growth factor beta) receptor] plays a crucial role in the TGF-beta signalling pathway. Although N-linked glycosylation of T beta R11 was first demonstrated over a decade ago, it was unclear how this modification influenced T beta RII biology. In the present study, we show that inhibiting the N-linked glycosylation process successfully hinders binding of TGF-beta 1 to T beta RII and subsequently renders cells resistant to TGF-beta signalling. The lung cancer eel:. line A549, the gastric carcinoma cell line MKN1 and the immortal cell line HEK (human embryonic kidney)-293 exhibit reduced TGF-beta signalling when either treated with two inhibitors, including tunicamycin (a potent N-linked glycosylation inhibitor) and kifunensine [an inhibitor of ER (endoplasmic reticulum) and Golgi mannosidase I family members], or introduced with a non-glycosylated mutant version of T beta RII. We demonstrate that defective N-linked glycosylation prevents T beta RII proteins from being transported to the cell surface. Moreover, we clearly show that not only the complex type, but also a high-mannose type, of T beta RII can be localized on the cell surface. Collectively, these findings demonstrate that N-linked glycosylation is essentially required for the successful cell surface transportation of T beta RII, suggesting a novel mechanism by which the TGF-beta sensitivity can be regulated by N-linked glycosylation levels of T beta RII.
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