Endodermal differentiation of murine embryonic carcinoma cells by retinoic acid requires JLP, a JNK-scaffolding protein.
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.
Kashef
Kimia
K
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Xu
Hua
H
Reddy
E Premkumar
EP
Dhanasekaran
Danny N
DN
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018236:Carcinoma, Embryonal / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004707:Endoderm / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C468928:Spag9 protein, mouse; D014212:Tretinoin; D044365:GTP-Binding Protein alpha Subunits, G12-G13