Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Transforming growth factor beta (TGF-beta) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin in early Xenopus embryos. Here we report that TMEFF1 binds to the nodal coreceptor Cripto, but does not associate with either nodal or the type I ALK (activin receptor-like kinase) 4 receptor in coimmunoprecipitation assays. The inhibition of the nodal signaling by TMEFF1 in Xenopus ectodermal explants is rescued with wild-type but not mutant forms of Cripto. Furthermore, we show that the Cripto-FRL1-Cryptic (CFC) domain in Cripto, which is essential for its binding to ALK4, is also important for its interaction with TMEFF1. Our results demonstrate for the first time that nodal signaling can be regulated by a novel mechanism of blocking the Cripto coreceptor.
???displayArticle.pubmedLink???
14563676
???displayArticle.pmcLink???PMC280611 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Adamson,
Cripto: a tumor growth factor and more.
2002, Pubmed,
Xenbase
Adamson,
Cripto: a tumor growth factor and more.
2002,
Pubmed
,
Xenbase
Bartholin,
Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function.
2002,
Pubmed
Bianco,
Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells.
2002,
Pubmed
Bianco,
A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src.
2003,
Pubmed
Bianco,
Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor.
1999,
Pubmed
Brennan,
Nodal activity in the node governs left-right asymmetry.
2002,
Pubmed
Chang,
Regulation of nodal and BMP signaling by tomoregulin-1 (X7365) through novel mechanisms.
2003,
Pubmed
,
Xenbase
Chang,
A Xenopus type I activin receptor mediates mesodermal but not neural specification during embryogenesis.
1997,
Pubmed
,
Xenbase
Cheng,
EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1.
2003,
Pubmed
,
Xenbase
Conlon,
A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse.
1994,
Pubmed
Eib,
A novel transmembrane protein with epidermal growth factor and follistatin domains expressed in the hypothalamo-hypophysial axis of Xenopus laevis.
1996,
Pubmed
,
Xenbase
Eimon,
Effects of heterodimerization and proteolytic processing on Derrière and Nodal activity: implications for mesoderm induction in Xenopus.
2002,
Pubmed
,
Xenbase
Gery,
TMEFF2 is an androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cells.
2002,
Pubmed
Gery,
TMEFF1 and brain tumors.
2003,
Pubmed
,
Xenbase
Glynne-Jones,
TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence.
2001,
Pubmed
Gray,
Cripto forms a complex with activin and type II activin receptors and can block activin signaling.
2003,
Pubmed
Gritsman,
The EGF-CFC protein one-eyed pinhead is essential for nodal signaling.
1999,
Pubmed
,
Xenbase
Harland,
Formation and function of Spemann's organizer.
1997,
Pubmed
Horie,
Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons.
2000,
Pubmed
Kogawa,
Activin-binding protein is present in pituitary.
1991,
Pubmed
López-Casillas,
Betaglycan presents ligand to the TGF beta signaling receptor.
1993,
Pubmed
Lowe,
Genetic dissection of nodal function in patterning the mouse embryo.
2001,
Pubmed
Massagué,
TGF-beta signal transduction.
1998,
Pubmed
Massagué,
Controlling TGF-beta signaling.
2000,
Pubmed
Normanno,
The role of EGF-related peptides in tumor growth.
2001,
Pubmed
Norris,
The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo.
2002,
Pubmed
Onichtchouk,
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
1999,
Pubmed
,
Xenbase
Piccolo,
The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.
1999,
Pubmed
,
Xenbase
Reissmann,
The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.
2001,
Pubmed
,
Xenbase
Sakuma,
Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion.
2002,
Pubmed
,
Xenbase
Schier,
Nodal signalling in vertebrate development.
2000,
Pubmed
Schneyer,
Follistatin-related protein (FSRP): a new member of the follistatin gene family.
2001,
Pubmed
Shen,
The EGF-CFC gene family in vertebrate development.
2000,
Pubmed
Shi,
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
2003,
Pubmed
Siegel,
Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development.
2002,
Pubmed
Tsuchida,
Intracellular and extracellular control of activin function by novel regulatory molecules.
2001,
Pubmed
Whitman,
Nodal signaling in early vertebrate embryos: themes and variations.
2001,
Pubmed
,
Xenbase
Yan,
Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway.
2002,
Pubmed
Yeo,
Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms.
2001,
Pubmed
,
Xenbase
