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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

97 Scopus citations

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 language	English (US)
Pages (from-to)	1192-1197
Number of pages	6
Journal	Cancer Research
Volume	63
Issue number	6
State	Published - Mar 15 2003
Externally published	Yes

Funding

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

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

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.",

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

year = "2003",

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day = "15",

language = "English (US)",

volume = "63",

pages = "1192--1197",

journal = "Cancer Research",

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T1 - A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src

AU - Bianco, Caterina

AU - Strizzi, Luigi

AU - Rehman, Aasia

AU - Normanno, Nicola

AU - Wechselberger, Christian

AU - Sun, Youping

AU - Khan, Nadia

AU - Hirota, Morihisa

AU - Adkins, Heather

AU - Williams, Kevin

AU - Margolis, Richard U.

AU - Sanicola, Michele

AU - Salomon, David S.

PY - 2003/3/15

Y1 - 2003/3/15

N2 - 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.

AB - 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.

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M3 - Article

C2 - 12649175

AN - SCOPUS:0037444172

SN - 0008-5472

VL - 63

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JO - Cancer Research

JF - Cancer Research

IS - 6

ER -

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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