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  • Title: Endodermal differentiation of murine embryonic carcinoma cells by retinoic acid requires JLP, a JNK-scaffolding protein.
    Author: Kashef K, Xu H, Reddy EP, Dhanasekaran DN.
    Journal: J Cell Biochem; 2006 Jul 01; 98(4):715-22. PubMed ID: 16619266.
    Abstract:
    Retinoic acid (RA) is a morphogen that induces endodermal differentiation of murine P19 embryonic carcinoma cells. RA-induced differentiation of P19 cells has been used as a model system to define the differentiation programs of pluripotent stem cells. Using this system it has been shown that G alpha13--the alpha-subunit of the heterotrimeric G protein G13--and its activation of JNK-module are critically required for the endodermal differentiation of P19 cells. However, the mechanism through which G alpha13 is linked to JNK-module is unknown. Here, we report that RA stimulates the expression of JNK-interacting leucine zipper protein (JLP), a newly identified JNK-scaffolding protein and its critical role in RA-mediated endodermal differentiation. Our results indicate that there is a physical association between JLP and G alpha13 in RA-stimulated P19 cells. More interestingly, silencing JLP abrogates RA-mediated endodermal differentiation of P19 cells analogous to the effects seen with the silencing of G alpha13 or JNK. Therefore, our studies presented here identify for the first time, a novel role for a newly identified scaffolding protein in RA-mediated endodermal differentiation, providing a new signaling conduit to transmit signals from RA to JNK module.
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