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Proline-rich Akt substrate of 40 kDa (PRAS40): A novel downstream target of PI3k/Akt signaling pathway
Wang, HT1; Zhang, QS1; Wen, Q1; Zheng, YX2; Philip, L3; Jiang, H4; Lin, J5; Zheng, WH1
2012
Source PublicationCELLULAR SIGNALLING
ISSN0898-6568
Volume24Issue:1Pages:17-24
Abstract

Modifications in signaling of the proline-rich Akt substrate of 40-kDa (PRAS40) pathway is implicated in type 2 diabetes and melanoma. PRAS40 is known for its ability to regulate the mammalian target ofrapamycin complex 1 (mTORC1) kinase activity, possessing a key regulatory role at the cross point ofsignal transduction pathways activated by growth factor receptors. Recently it has been found that PRAS40 is regulated by its upstream phosphatidylinositol 3-kinase/Akt (PI3K/Akt) which is activated by many tyrosine kinase receptors growth factors including insulin-like growth factor 1. Also, PRAS40functions downstream of mTORC1 and upstream from its effectors ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Phosphorylation of PRAS40 by Akt and mTORC1 disrupts the binding between mTORC1 and PRAS40, and relieves the inhibitory constraint of PRAS40 on mTORC1 activity. This review summarizes the signaling regulating PRAS40phosphorylation, as well as the dual function of PRAS40 as substrate and inhibitor of mTORC1 upon growth factor stimulation and under pathophysiological conditions. (C) 2011 Elsevier Inc. All rights reserved.

KeywordPras40 Tumorigenesis Insulin Resistance Pi3k/akt Mtorc1
DOIhttps://dx.doi.org/10.1016/j.cellsig.2011.08.010
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000297392900003
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Cited Times [WOS]:90   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510006, Guangdong, Peoples R China
3.Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Inst Drug Res, IL-91120 Jerusalem, Israel
4.Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
5.Suny Downstate Med Ctr, Dept Anesthesiol, Brooklyn, NY 11203 USA
Recommended Citation
GB/T 7714
Wang, HT,Zhang, QS,Wen, Q,et al. Proline-rich Akt substrate of 40 kDa (PRAS40): A novel downstream target of PI3k/Akt signaling pathway[J]. CELLULAR SIGNALLING,2012,24(1):17-24.
APA Wang, HT.,Zhang, QS.,Wen, Q.,Zheng, YX.,Philip, L.,...&Zheng, WH.(2012).Proline-rich Akt substrate of 40 kDa (PRAS40): A novel downstream target of PI3k/Akt signaling pathway.CELLULAR SIGNALLING,24(1),17-24.
MLA Wang, HT,et al."Proline-rich Akt substrate of 40 kDa (PRAS40): A novel downstream target of PI3k/Akt signaling pathway".CELLULAR SIGNALLING 24.1(2012):17-24.
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