PRAS40, which stands for Proline-rich Akt Substrate of 40 kDa, is a multifunctional protein that plays various roles within the cell, especially in biological processes such as cell growth, apoptosis, oxidative stress, autophagy, and angiogenesis. PRAS40 is a substrate of the protein kinase B (PKB/Akt) and also a binding protein for 14-3-3 proteins. It is expressed in a variety of tissues and has multiple phosphorylation sites, with its activity closely related to its phosphorylation status. PRAS40 is involved in several signaling pathways, including the mammalian target of rapamycin (mTOR) pathway, the protein kinase B (PKB/Akt) pathway, nuclear factor kappa-B (NF-κB), proto-oncogene serine/threonine-protein kinase PIM-1 (PIM1), and pyruvate kinase M2 (PKM2). PRAS40 plays a significant role in a variety of human diseases, including cardiovascular diseases, ischemia-reperfusion injury, neurodegenerative diseases, cancer, diabetes, and other metabolic diseases. Moreover, the nuclear localization of PRAS40 is associated with the Akt/mTORC1 signaling axis and the RPL11-HDM2-p53 nucleolar stress response pathway. The phosphorylation of PRAS40, especially at the Thr246 site, mediated by Akt and mTORC1, may have an important impact on mTORC1 activity.
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