Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 16 October 2001
Vol. 2001, Issue 104, p. tw376
[DOI: 10.1126/stke.2001.104.tw376]


Glycosylation Fucosylation Required

Glycosylation of proteins by the addition of O-linked fucose is rare and, so far, has been reported only for proteins containing an epidermal growth factor (EGF)-like domain. Schiffer et al. showed that the human EGF-CFC protein cripto, which has an EGF-like domain and a cysteine-rich domain, is O-fucosylated on residue Thr88 and that this modification is essential for cripto to serve as a signaling cofactor for transforming growth factor-β (TGF-β). O-Fucosylation was determined by mass spectroscopy. Activity of both cripto and the fucosylation-deficient mutant Thr88Ala (T88A) was assessed in mouse cell lines null for the mouse member of the EGF-CFC family and in Xenopus embryos. Exposure of the mouse cells transfected with the T88A mutant to TGF-β did not stimulate the expression of a reporter gene specific for the combined cripto and TGF-β signal, whereas wild-type cripto did stimulate expression in the presence of TGF-β. Analysis of embryo explants from Xenopus injected with RNA for wild-type or T88A cripto demonstrated that fucosylation was essential to stimulate Smad2 phosphorylation, an intermediate in the signaling pathway mediated by TGF-β and cripto. Thus, O-fucosylation joins the other glycosylation modifications that regulate signaling protein function and activity.

S. G. Schiffer, S. Foley, A. Kaffashan, X. Hronowski, A. E. Zichittella, C.-Y. Yeo, K. Miatkowski, H. B. Adkins, B. Damon, M. Whitman, D. Salomon, M. Sanicola, K. P. Williams, Fucosylation of cripto is required for its ability to facilitate nodal signaling. J. Biol. Chem. 276, 37769-37778 (2001). [Abstract] [Full Text]

Citation: Fucosylation Required. Sci. STKE 2001, tw376 (2001).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882