Endodermal differentiation of murine embryonic carcinoma cells by retinoic acid requires JLP, a JNK-scaffolding protein

Kimia Kashef, Hua Xu, E. Premkumar Reddy, Danny N. Dhanasekaran

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 Gα13-the α-subunit of the heterotrimeric G protein G 13-and its activation of JNK-module are critically required for the endodermal differentiation of P19 cells. However, the mechanism through which Gα13 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 Gα13 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 Gα13 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.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
JournalJournal of Cellular Biochemistry
Volume98
Issue number4
DOIs
StatePublished - 1 Jul 2006
Externally publishedYes

Keywords

  • Endodermal differentiation
  • G protein
  • JLP
  • JNK
  • Scaffolding protein
  • Stem cell

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