Kashef Kimia, Xu Hua, Reddy E Premkumar, Dhanasekaran Danny N
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
J Cell Biochem. 2006 Jul 1;98(4):715-22. doi: 10.1002/jcb.20930.
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.
视黄酸（RA）是一种形态发生素，可诱导小鼠P19胚胎癌细胞向内胚层分化。RA诱导的P19细胞分化已被用作定义多能干细胞分化程序的模型系统。利用该系统已表明，异源三聚体G蛋白G13的α亚基Gα13及其对JNK模块的激活对于P19细胞的内胚层分化至关重要。然而，Gα13与JNK模块相连的机制尚不清楚。在此，我们报告RA刺激JNK相互作用亮氨酸拉链蛋白（JLP）的表达，JLP是一种新鉴定的JNK支架蛋白，其在RA介导的内胚层分化中起关键作用。我们的结果表明，在RA刺激的P19细胞中，JLP与Gα13之间存在物理关联。更有趣的是，沉默JLP可消除RA介导的P19细胞内胚层分化，类似于沉默Gα13或JNK所观察到的效果。因此，我们在此提出的研究首次确定了一种新鉴定的支架蛋白在RA介导的内胚层分化中的新作用，提供了一种从RA向JNK模块传递信号的新信号传导途径。
