Premium
Cripto/GRP78 modulation of the TGF‐β pathway in development and oncogenesis
Author(s) -
Gray Peter C.,
Vale Wylie
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.01.051
Subject(s) - microbiology and biotechnology , pi3k/akt/mtor pathway , signal transduction , mapk/erk pathway , carcinogenesis , nodal signaling , biology , protein kinase b , proto oncogene tyrosine protein kinase src , transforming growth factor , chemistry , cancer research , genetics , embryogenesis , cancer , gastrulation , embryo
Cripto is a small, GPI‐anchored signaling protein that regulates cellular survival, proliferation, differentiation and migration during normal developmental processes and tumorigenesis. Cripto functions as an obligatory co‐receptor for the TGF‐β ligands Nodal, GDF1 and GDF3 but attenuates signaling of others such as activin‐A, activin‐B and TGF‐β1. Soluble, secreted forms of Cripto also activate Src, ras/raf/MAPK and PI3K/Akt pathways via a mechanism that remains largely obscure. This review describes the biological roles and signaling mechanisms of Cripto, highlighting our identification of the 78 kDa glucose regulated protein (GRP78) as a cell surface receptor/co‐factor required for Cripto signaling via both TGF‐β and Src/MAPK/PI3K pathways. We discuss emerging evidence indicating that Cripto/GRP78 signaling regulates normal somatic stem cells and their tumorigenic counterparts.