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These physiological roles of Akt include involvement in metabolism, protein synthesis, apoptosis pathways, transcription factor regulation and the cell cycle. Akt exerts its effects in the cell by phosphorylating a variety of downstream substrates. The downstream targets of Akt include BAD (BCL2 Antagonist of Cell Death), Caspase9, FKHR (Forkhead Transcriptional Factor), GLUTs (Glucose Transporters), eNOS (Nitric Oxide Synthase), PFK2 (6-Phosphofructo-2-Kinase), PFK1(6-Phosphofructo-Kinase), mTOR (Mammalian Target of Rapamycin), IKK (I-KappaB Kinase), NF-KappaB (Nuclear Factor-KappaB), GSK3 (Glycogen Synthase Kinase-3), WNK1(WNK Lysine deficient Protein Kinase-1), PRAS40 (Proline-Rich Akt Substrate.
"Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis. "Huang B. , Porter G. Acta Pharmacol. Sin.
mTOR is a master integrator of signals governing protein and lipid biosynthesis and growth factor–driven cell cycle progression (Figure 1). It functions to regulate these processes in two cellular complexes. mTOR complex 1 (mTORC1) includes mTOR regulatory-associated protein of mTOR (Raptor), mLST8, and proline-rich Akt substrate.
Reduced TSC2 (also called tuberin) together with loss of TSC1 (also known as hamartin) is frequently found in TSC, an autosomal dominant tumor disease affecting 1 in 6000 individuals. TSC2 phosphorylation by Akt induces the activity of mTORC1 by relieving Ras enriched in brain (Rheb) GTPase from the inhibition of the TSC1/TSC2 complex (Tee et al. , 2003). A second binding partner of mTOR and also a substrate for Akt is proline-rich Akt substrate.
50 - N. Oshiro, R. Takahashi, K. Yoshino, K. Tanimura, A. Nakashima, et al. 2007The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. The Journal of biological chemistry. 282282032939Epub 2007/05/23.