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

EDITORS' CHOICE

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).


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