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  • Title: A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src.
    Author: Bianco C, Strizzi L, Rehman A, Normanno N, Wechselberger C, Sun Y, Khan N, Hirota M, Adkins H, Williams K, Margolis RU, Sanicola M, Salomon DS.
    Journal: Cancer Res; 2003 Mar 15; 63(6):1192-7. PubMed ID: 12649175.
    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 beta-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.
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