The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling.

The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Research Abstract Details 

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The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Abstract Text:

Shaolin Shi,Changhui Ge,Yi Luo,Xinghua Hou,Robert S Haltiwanger,Pamela Stanley,

Cripto is a membrane-bound co-receptor for Nodal, a member of the transforming growth factor-beta superfamily. Mouse embryos lacking either Cripto or Nodal have the same lethal phenotype at embryonic day 7.5. Previous studies suggest that O-fucosylation of the epidermal growth factor-like (EGF) repeat in Cripto is essential for the facilitation of Nodal signaling. Substitution of Ala for the Thr to which O-fucose is attached led to functional inactivation of both human and mouse Cripto. However, embryos null for protein O-fucosyltransferase 1, the enzyme that adds O-fucose to EGF repeats, do not exhibit a Cripto null phenotype and die at about embryonic day 9.5. This suggested that the loss of O-fucose from the EGF repeat may not have led to the inactivation of Cripto in previous studies. Here we investigate this hypothesis and show the following: 1) protein O-fucosyltransferase 1 is indeed the enzyme that adds O-fucose to Cripto; 2) Pofut1(-/-) embryonic stem cells behave the same as Pofut1(+/+) embryonic stem cells in a Nodal signaling assay; 3) Pofut1(-/-) and Pofut1(+/+) embryoid bodies are indistinguishable in their ability to differentiate into cardiomyocytes; and 4) none of 10 amino acid substitutions at Thr(72), including Ser which acquires O-fucose, rescues the activity of mouse Cripto in Nodal signaling assays. Therefore, the Thr to which O-fucose is linked in Cripto plays a key functional role, but O-fucose at Thr(72) is not required for Cripto to function in cell-based signaling assays or in vivo. By contrast, we show that O-fucose, and not the Thr to which it is attached, is required in the ligand-binding domain of Notch1 for Notch1 signaling.

The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Publishing Authors By Initials

S Shi,C Ge,Y Luo,X Hou,RS Haltiwanger,P Stanley,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 20133-41

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 15

MONTH: 05

YEAR: 2007

The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: metabolism

Chemical & Substance for Abstract: The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling. Information

Substance Name: Fucosyltransferases

Registry Number: EC 2.4.1.-

Grant and Affiliation Information for The threonine that carries fucose, but not fucose, is required for Cripto to facilitate Nodal signaling.

AFFILIATION: Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA.

Country: United States

AGENCY: United States PHS

GRANT: P01 13330

ACRONYM: GM

MEDLINETA: J Biol Chem

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