A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src

Caterina Bianco, Luigi Strizzi, Aasia Rehman, Nicola Normanno, Christian Wechselberger, Youping Sun, Nadia Khan, Morihisa Hirota, Heather Adkins, Kevin Williams, Richard U. Margolis, Michele Sanicola, David S. Salomon

Research output: Contribution to journalArticle

Abstract

Human Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto FRL1 Cryptic family that has been shown to function as a coreceptor with the type I Activin serine-threonine kinase receptor ALK4 for the transforming growth factor β-related peptide Nodal. However, CR-1 can also activate the mitogen-activated protein kinase and Akt pathways independently of Nodal and ALK4 by an unknown mechanism. Here, we demonstrate that CR-1 specifically binds to Glypican-1, a membrane-associated heparan sulfate proteoglycan, and activates the tyrosine kinase c-Src, triggering the mitogen-activated protein kinase and Akt signaling pathways. Finally, an active Src kinase is necessary for CR-1 to induce in vitro transformation and migration in mouse mammary epithelial cells.

Original languageEnglish
Pages (from-to)1192-1197
Number of pages6
JournalCancer Research
Volume63
Issue number6
Publication statusPublished - Mar 15 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src'. Together they form a unique fingerprint.

Cite this