title: Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway.
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 of rapamycin complex 1 (mTORC1) kinase activity, possessing a key regulatory role at the cross point of signal 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, PRAS40 functions 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 PRAS40 phosphorylation, as well as the dual function of PRAS40 as substrate and inhibitor of mTORC1 upon growth factor stimulation and under pathophysiological conditions.
authors: Neuropharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors: Haitao
authors: H
authors: Wang
authors: Qishan
authors: Q
authors: Zhang
authors: Qiang
authors: Q
authors: Wen
authors: Yongxin
authors: Y
authors: Zheng
authors: Philip
authors: P
authors: Lazarovici
authors: Lazarovici
authors: L
authors: Philip
authors: Hao
authors: H
authors: Jiang
authors: Jun
authors: J
authors: Lin
authors: WenHua
authors: W
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D000076222:Mechanistic Target of Rapamycin Complex 1; D008545:Melanoma / Q000378:metabolism / Q000503:physiopathology; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000503:physiopathology; D008579:Meningioma / Q000378:metabolism / Q000503:physiopathology; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C484523:AKT1S1 protein, human