Document Detail

Endodermal differentiation of murine embryonic carcinoma cells by retinoic acid requires JLP, a JNK-scaffolding protein.
MedLine Citation:
PMID:  16619266     Owner:  NLM     Status:  MEDLINE    
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.
Kimia Kashef; Hua Xu; E Premkumar Reddy; Danny N Dhanasekaran
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  98     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-29     Completed Date:  2006-08-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  715-22     Citation Subset:  IM    
Copyright Information:
2006 Wiley-Liss, Inc.
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
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MeSH Terms
Adaptor Proteins, Signal Transducing / metabolism*
Antineoplastic Agents / pharmacology*
Carcinoma, Embryonal / metabolism*
Cell Differentiation / drug effects*
Cell Line, Tumor
Endoderm / metabolism*
GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
Models, Biological*
Pluripotent Stem Cells / metabolism*
Signal Transduction / drug effects
Tretinoin / pharmacology*
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antineoplastic Agents; 0/Spag9 protein, mouse; 302-79-4/Tretinoin; EC Protein alpha Subunits, G12-G13

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