Anti-Proline-rich AKT1 substrate 1 AKT1S1 Antibody

The Akt signaling pathway contributes to the regulation of apoptosis after a variety of cell death signals. AKT1S1, also known as PRAS40, is a proline-rich substrate of the kinase AKT1 and is thought to play a role in neuroprotection mediated by nerve growth factor (NGF) after transient focal cerebral ischemia (1) . AKT1S1 is also a substrate and potential regulator of mammalian target of rapamycin (mTOR), a serine/threonine kinase that regulates cell growth and cell cycle, and a negative regulator of autophagy (2) . Treatment with the insulin-like growth factor-1 (IGF1) can indusce the phosphorylation of AKT1S1 via the PI3K/AKT signaling pathway in PC12 cells (3) .

AKT1S1 antibody was raised against a 19 amino acid peptide near the carboxy terminus of human AKT1S1. The immunogen is located within amino acids 190 - 240 of AKT1S1.

Widely expressed with highest levels of expression in liver and heart. Expressed at higher levels in cancer cell lines (e.g. A-549 and HeLa) than in normal cell lines (e.g. HEK293) .

Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E) . mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.