84-9372-50　［取扱停止］Recombinant Mouse AKT1 Protein （His Tag） 20ug　PKSM041378

特徴

• 背景：AKT1 is one of 3 closely related serine/threonine-protein kinases （AKT1, AKT2 and AKT3） called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
• This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates.
• Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported.
• AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface.
• Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling.
• Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport.
• AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity.
• Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven.
• AKT regulates also cell survival via the phosphorylation of MAP3K5 （apoptosis signal-related kinase）.
• Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis.
• AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1.
• AKT is involved in the phosphorylation of members of the FOXO factors （Forkhead family of transcription factors）, leading to binding of 14-3-3 proteins and cytoplasmic localization.
• In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'.
• FOXO3 and FOXO4 are phosphorylated on equivalent sites.
• AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 （cyclic AMP （cAMP）-response element binding protein）.
• The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1.
• AKT phosphorylates 'Ser-454' on ATP citrate lyase （ACLY）, thereby potentially regulating ACLY activity and fatty acid synthesis.
• Activates the 3B isoform of cyclic nucleotide phosphodiesterase （PDE3B） via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis.
• Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI3P-5 activity.
• The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth.
• AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation.
• Signals downstream of phosphatidylinositol 3-kinase （PI3K） to mediate the effects of various growth factors such as platelet-derived growth factor （PDGF）, epidermal growth factor （EGF）, insulin and insulin-like growth factor I （IGF-I）.
• AKT mediates the antiapoptotic effects of IGF-I.
• Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly.
• May be involved in the regulation of the placental development.
• Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its： kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3.
• Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its： cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation.
• Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation （By similarity）.
• Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity （By similarity）.
• Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 （By similarity）.