| Literature DB >> 30154443 |
Youming Zhu1, Peng Wang2, Li Zhang3, Guo Bai4, Chi Yang4, Yuanying Wang1, Jiacai He1, Zhiyuan Zhang4, Guoping Zhu5, Duohong Zou6,7.
Abstract
Embryonic stem cells (ESCs) hold great promise for regenerative medicine. To harness the full therapeutic potential of ESCs, better understanding of the molecular mechanisms underlying the maintenance and differentiation of ESCs is required. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that integrates growth factor receptor signaling with cellular growth and proliferation. Dysregulation of mTOR signaling has been linked to various human diseases including cancer and metabolic syndromes. However, little is known regarding the function of mTOR signaling in the regulation of ES cell differentiation. Here we report that Rictor, a key component of mTORC2, functions as a novel ES cell differentiation promoting factor. Mechanistically, Rictor is able to interact with Prkch and facilitate Prkch phosphorylation at Ser-642. Upon phosphorylation, Prkch promotes Klf4 phosphorylation and inhibits Klf4-dependent E-cadherin expression, thereafter leading to the ES cell differentiation. These findings reveal a novel Rictor-Prkch-Klf4 pathway that plays an important role in the regulation of ES cell differentiation.Entities:
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Year: 2018 PMID： 30154443 PMCID： PMC6461888 DOI： 10.1038/s41418-018-0177-5
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 15.828