Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1

Kazuhide Watanabe, Tadahiro Nagaoka, Joseph M. Lee, Caterina Bianco, Monica Gonzales, Nadia P. Castro, Maria Cristina Rangel, Kei Sakamoto, Youping Sun, Robert Callahan, David S. Salomon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Nodal and Notch signaling pathways play essential roles in vertebrate development. Through a yeast two-hybrid screening, we identified Notch3 as a candidate binding partner of the Nodal coreceptor Cripto-1. Coimmunoprecipitation analysis confirmed the binding of Cripto-1 with all four mammalian Notch receptors. Deletion analyses revealed that the binding of Cripto-1 and Notch1 is mediated by the Cripto-1/ FRL-1/Cryptic domain of Cripto-1 and the C-terminal region of epidermal growth factor-like repeats of Notch1. Binding of Cripto-1 to Notch1 occurred mainly in the endoplasmic reticulum-Golgi network. Cripto-1 expression resulted in the recruitment of Notch1 protein into lipid raft microdomains and enhancement of the furin-like protein convertase-mediated proteolytic maturation of Notch1 (S1 cleavage). Enhanced S1 cleavage resulted in the sensitization to ligand-induced activation of Notch signaling. In addition, knockdown of Cripto-1 expression in human and mouse embryonal carcinoma cells desensitized the ligand-induced Notch signaling activation. These results suggest a novel role of Cripto-1 in facilitating the posttranslational maturation of Notch receptors.

Original languageEnglish
Pages (from-to)343-353
Number of pages11
JournalJournal of Cell Biology
Volume187
Issue number3
DOIs
Publication statusPublished - 02-11-2009

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Notch Receptors
Notch1 Receptor
Furin
Ligands
Embryonal Carcinoma Stem Cells
Epidermal Growth Factor
Endoplasmic Reticulum
Vertebrates
Yeasts
Lipids

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Watanabe, K., Nagaoka, T., Lee, J. M., Bianco, C., Gonzales, M., Castro, N. P., ... Salomon, D. S. (2009). Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1. Journal of Cell Biology, 187(3), 343-353. https://doi.org/10.1083/jcb.200905105
Watanabe, Kazuhide ; Nagaoka, Tadahiro ; Lee, Joseph M. ; Bianco, Caterina ; Gonzales, Monica ; Castro, Nadia P. ; Rangel, Maria Cristina ; Sakamoto, Kei ; Sun, Youping ; Callahan, Robert ; Salomon, David S. / Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1. In: Journal of Cell Biology. 2009 ; Vol. 187, No. 3. pp. 343-353.
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Watanabe, K, Nagaoka, T, Lee, JM, Bianco, C, Gonzales, M, Castro, NP, Rangel, MC, Sakamoto, K, Sun, Y, Callahan, R & Salomon, DS 2009, 'Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1', Journal of Cell Biology, vol. 187, no. 3, pp. 343-353. https://doi.org/10.1083/jcb.200905105

Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1. / Watanabe, Kazuhide; Nagaoka, Tadahiro; Lee, Joseph M.; Bianco, Caterina; Gonzales, Monica; Castro, Nadia P.; Rangel, Maria Cristina; Sakamoto, Kei; Sun, Youping; Callahan, Robert; Salomon, David S.

In: Journal of Cell Biology, Vol. 187, No. 3, 02.11.2009, p. 343-353.

Research output: Contribution to journalArticle

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AU - Salomon, David S.

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