TY - JOUR
T1 - Cripto-1 activates Nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial cells
AU - Bianco, Caterina
AU - Adkins, Heather B.
AU - Wechselberger, Christian
AU - Seno, Masaharu
AU - Normanno, Nicola
AU - De Luca, Antonella
AU - Sun, Youping
AU - Khan, Nadia
AU - Kenney, Nicholas
AU - Ebert, Andreas
AU - Williams, Kevin P.
AU - Sanicola, Michele
AU - Salomon, David S.
PY - 2002
Y1 - 2002
N2 - Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor β family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.
AB - Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor β family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.
UR - http://www.scopus.com/inward/record.url?scp=0036210652&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036210652&partnerID=8YFLogxK
U2 - 10.1128/MCB.22.8.2586-2597.2002
DO - 10.1128/MCB.22.8.2586-2597.2002
M3 - Article
C2 - 11909953
AN - SCOPUS:0036210652
SN - 0270-7306
VL - 22
SP - 2586
EP - 2597
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 8
ER -