Fucosylation of Cripto is Required for its Ability to Facilitate Nodal Signaling

Susan G. Schiffer, Susan Foley, Azita Kaffashan, Xiaoping Hronowski, Anne E. Zichittella, Chang Yeol Yeo, Konrad Miatkowski, Heather B. Adkins, Bruno Damon, Malcolm Whitman, David Salomon, Michele Sanicola, Kevin P. Williams

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

O-Linked fucose modification is rare and has been shown to occur almost exclusively within epidermal growth factor (EGF)-like modules. We have found that the EGF-CFC family member human Cripto-1 (CR) is modified with fucose and through a combination of peptide mapping, mass spectrometry, and sequence analysis localized the site of attachment to Thr-88. The identification of a fucose modification on human CR within its EGF-like domain and the presence of a consensus fucosylation site within all EGF-CFC family members suggest that this is a biologically important modification in CR, which functionally distinguishes it from the EGF ligands that bind the type 1 erbB growth factor receptors. A single CR point mutation, Thr-88 → Ala, results in a form of the protein that is not fucosylated and has substantially weaker activity in cell-based CR/Nodal signaling assays, indicating that fucosylation is functionally important for CR to facilitate Nodal signaling.

Original languageEnglish
Pages (from-to)37769-37778
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number41
StatePublished - 12 Oct 2001

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