Abstract
The proline-rich Akt substrate of 40 kDa (PRAS40) is a substrate of Akt and a component of the mammalian target of rapamycin complex 1 (mTORC1). Locating at the crossroad of the PI3K/Akt pathway and the mTOR pathway, PRAS40 is phosphorylated by growth factors or other stimuli, and regulates the activation of these signaling pathways in turn. PRAS40 plays an important role in metabolic disorders and multiple cancers, and the phosphorylation of PRAS40 is often associated with the tumor progression of melanoma, prostate cancer, etc. PRAS40 promotes tumorigenesis by deregulating cellular proliferation, apoptosis, senescence, metastasis, etc. Herein, we provide an overview on current understandings of PRAS40 signaling in the tumor formation and progression, which suggests that PRAS40 or phospho-PRAS40 could become a novel biomarker and therapeutic target in tumor.
Highlights
The proline-rich Akt substrate of 40 kDa (PRAS40) is encoded by AKT1S1 (Akt1 substrate 1) which locates on the chromosome 19q13.33. 15% of PRAS40’s amino acids are prolines, but the function of the two proline-enriched stretches at the N-terminal region remains unknown
In response to the treatment of growth factors, PRAS40 is phosphorylated on Thr246 by Akt, and phosphorylated on Ser183 and Ser221 by mammalian target of rapamycin (mTOR) (Figure 1A), all of which are essential to the dissociation of PRAS40 from the mammalian target of rapamycin complex 1 (mTORC1) and the binding of PRAS40 to the cellular anchor protein 14-3-3 in HEK293 cells and fibroblasts [1, 2, 34, 49, 50]
Similar as other adaptor proteins, such as Grb2 and Crk, PRAS40 binds to a couple of factors and links several important signaling pathways especially phosphatidylinositol 3-kinase (PI3K)/Akt and mTOR pathways
Summary
The proline-rich Akt substrate of 40 kDa (PRAS40) is encoded by AKT1S1 (Akt1 substrate 1) which locates on the chromosome 19q13.33. 15% of PRAS40’s amino acids are prolines, but the function of the two proline-enriched stretches at the N-terminal region remains unknown. PRAS40 is phosphorylated in response to insulin or IGF-1 treatment, and plays an important role in the tumor cell proliferation induced by these growth factors [22, 25].
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