Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation.

作者: Wei-Yen Chen , Chia-Lung Lin , Jen-Hua Chuang , Fu-Yu Chiu , Yun-Ya Sun

DOI: 10.1038/SREP41159

关键词: Heterogeneous Nuclear Ribonucleoprotein MProtein kinase BImmunoprecipitationPI3K/AKT/mTOR pathwaymTORC1mTORC2Cell biologyChemistryPhosphorylationC2C12

摘要: Mammalian target of rapamycin (mTOR) plays a range crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, complex 1 2 (mTORC1 mTORC2), via association with series different components; this allows the complexes to execute their wide functions. This study explores further composition mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation mass spectrometry, novel associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The between hnRNP verified using recombinant endogenous protein binding site found be within aa 1~532 M. presence significantly affects phosphorylation SGK1 S422, but not Akt S473, PKCα S657 PKCζ T560. Furthermore, also critical role muscle differentiation because knock-down either or C2C12 myoblasts reduced differentiation. decrease is able rescued by overexpression SGK S422D knockdown myoblasts. Taken together, we have identified Rictor/mTOR molecule, M, that signaling phosphorylate thus regulating

参考文章(44)
Margit Rosner, Markus Hengstschläger, Detection of Cytoplasmic and Nuclear Functions of mTOR by Fractionation Methods in Molecular Biology. ,vol. 821, pp. 105- 124 ,(2012) , 10.1007/978-1-61779-430-8_8
Joel Escobedo, Timothy J. Koh, Improved transfection technique for adherent cells using a commercial lipid reagent. BioTechniques. ,vol. 35, pp. 936- 940 ,(2003) , 10.2144/03355BM06
Nadera Ainaoui, Fransky Hantelys, Edith Renaud-Gabardos, Morgane Bunel, Frédéric Lopez, Françoise Pujol, Remi Planes, Elmostafa Bahraoui, Carole Pichereaux, Odile Burlet-Schiltz, Angelo Parini, Barbara Garmy-Susini, Anne-Catherine Prats, Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation PLOS ONE. ,vol. 10, pp. e0136466- ,(2015) , 10.1371/JOURNAL.PONE.0136466
Guri Tzivion, Melissa Dobson, Gopalakrishnan Ramakrishnan, FoxO transcription factors; Regulation by AKT and 14-3-3 proteins Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. ,vol. 1813, pp. 1938- 1945 ,(2011) , 10.1016/J.BBAMCR.2011.06.002
Ronald W. Matheny, Christine M. Lynch, Luis A. Leandry, Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110β-deficient myoblasts is mediated by PI3K p110α and mTORC2 Growth Factors Journal. ,vol. 30, pp. 367- 384 ,(2012) , 10.3109/08977194.2012.734507
Christian C. Dibble, Winfried Elis, Suchithra Menon, Wei Qin, Justin Klekota, John M. Asara, Peter M. Finan, David J. Kwiatkowski, Leon O. Murphy, Brendan D. Manning, TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1 Molecular Cell. ,vol. 47, pp. 535- 546 ,(2012) , 10.1016/J.MOLCEL.2012.06.009
Siew Ping Han, Yue Hang Tang, Ross Smith, Functional diversity of the hnRNPs: past, present and perspectives. Biochemical Journal. ,vol. 430, pp. 379- 392 ,(2010) , 10.1042/BJ20100396
Margit Rosner, Markus Hengstschläger, mTOR protein localization is cell cycle-regulated. Cell Cycle. ,vol. 10, pp. 3608- 3610 ,(2011) , 10.4161/CC.10.20.17855
Ryan C. Russell, Ye Tian, Haixin Yuan, Hyun Woo Park, Yu-Yun Chang, Joungmok Kim, Haerin Kim, Thomas P. Neufeld, Andrew Dillin, Kun-Liang Guan, ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase Nature Cell Biology. ,vol. 15, pp. 741- 750 ,(2013) , 10.1038/NCB2757