PMID- 30154443 OWN - NLM STAT- MEDLINE DCOM- 20200706 LR - 20211204 IS - 1476-5403 (Electronic) IS - 1350-9047 (Print) IS - 1350-9047 (Linking) VI - 26 IP - 5 DP - 2019 May TI - Superhero Rictor promotes cellular differentiation of mouse embryonic stem cells. PG - 958-968 LID - 10.1038/s41418-018-0177-5 [doi] AB - 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. FAU - Zhu, Youming AU - Zhu Y AD - Department of Dental Implant Center, Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230022, China. FAU - Wang, Peng AU - Wang P AD - Institute of Molecular Biology and Biotechnology, College of Life Sciences, Anhui Normal University, No. 1 Beijing East Road, Wuhu, Anhui Province, 241000, China. FAU - Zhang, Li AU - Zhang L AUID- ORCID: 0000-0003-2599-952X AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui Province, 230022, China. FAU - Bai, Guo AU - Bai G AD - Department of Oral Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200001, China. FAU - Yang, Chi AU - Yang C AD - Department of Oral Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200001, China. FAU - Wang, Yuanying AU - Wang Y AD - Department of Dental Implant Center, Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230022, China. FAU - He, Jiacai AU - He J AD - Department of Dental Implant Center, Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230022, China. FAU - Zhang, Zhiyuan AU - Zhang Z AD - Department of Oral Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200001, China. FAU - Zhu, Guoping AU - Zhu G AD - Institute of Molecular Biology and Biotechnology, College of Life Sciences, Anhui Normal University, No. 1 Beijing East Road, Wuhu, Anhui Province, 241000, China. gpz1996@yahoo.com. FAU - Zou, Duohong AU - Zou D AD - Department of Dental Implant Center, Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230022, China. zdhyy@ahmu.edu.cn. AD - Department of Oral Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200001, China. zdhyy@ahmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180828 PL - England TA - Cell Death Differ JT - Cell death and differentiation JID - 9437445 RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Multiprotein Complexes) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (rictor protein, mouse) RN - EC 2.7.1.- (protein kinase C eta) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Animals MH - Cell Differentiation/*genetics MH - Cell Proliferation/genetics MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/*genetics MH - Mechanistic Target of Rapamycin Complex 2/genetics MH - Mice MH - Mouse Embryonic Stem Cells/cytology/*metabolism MH - Multiprotein Complexes/genetics MH - Phosphorylation/genetics MH - Protein Kinase C/*genetics MH - Rapamycin-Insensitive Companion of mTOR Protein/*genetics MH - Signal Transduction/genetics MH - TOR Serine-Threonine Kinases/genetics PMC - PMC6461888 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/08/30 06:00 MHDA- 2020/07/07 06:00 PMCR- 2020/05/01 CRDT- 2018/08/30 06:00 PHST- 2017/11/20 00:00 [received] PHST- 2018/07/13 00:00 [accepted] PHST- 2018/07/09 00:00 [revised] PHST- 2018/08/30 06:00 [pubmed] PHST- 2020/07/07 06:00 [medline] PHST- 2018/08/30 06:00 [entrez] PHST- 2020/05/01 00:00 [pmc-release] AID - 10.1038/s41418-018-0177-5 [pii] AID - 177 [pii] AID - 10.1038/s41418-018-0177-5 [doi] PST - ppublish SO - Cell Death Differ. 2019 May;26(5):958-968. doi: 10.1038/s41418-018-0177-5. Epub 2018 Aug 28.