AKT1 (S129) Blocking Peptide | AKT1 blocking peptide

Phospho-AKT1(S129) Antibody Blocking peptide

• Gene Names: AKT1; AKT; PKB; RAC; CWS6; PRKBA; PKB-ALPHA; RAC-ALPHA
• Synonyms: AKT1 (S129); Phospho-AKT1(S129) Antibody Blocking peptide; RAC-alpha serine/threonine-protein kinase; Protein kinase B; PKB; Protein kinase B alpha; PKB alpha; Proto-oncogene c-Akt; RAC-PK-alpha; AKT1; RAC; AKT1 blocking peptide

• Clone Number: 4103110
• Specificity: The synthetic peptide sequence used to generate the antibody was selected from the region of human Phospho-AKT1-S129. A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.
• Form/Format: The synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml deionized water for a final concentration of 1 mg/ml.
• Sequence Length: 480

• Function: 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 PI(3)P-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 (PI(3)K) 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. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro- apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.
• Cellular Location: Cytoplasm. Nucleus. Cell membrane. Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. Colocalizes with WDFY2 in intracellular vesicles (PubMed:16792529)
• Tissue Location: Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.
• Preparation and Storage: Maintain refrigerated at 2-8 degree C for up to 6 months. For long term storage store at -20 degree C.

Related Product Information for AKT1 blocking peptide

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery.

NCBI and Uniprot Product Information

• NCBI GI #: 60391226
• NCBI GeneID: 207
• UniProt Accession #: P31749; Q9BWB6; B2RAM5; B7Z5R1
• Molecular Weight: 48,347 Da
• NCBI Official Full Name: RAC-alpha serine/threonine-protein kinase
• NCBI Official Synonym Full Names: AKT serine/threonine kinase 1
• NCBI Official Symbol: AKT1
• NCBI Official Synonym Symbols: AKT; PKB; RAC; CWS6; PRKBA; PKB-ALPHA; RAC-ALPHA
• NCBI Protein Information: RAC-alpha serine/threonine-protein kinase
• UniProt Protein Name: RAC-alpha serine/threonine-protein kinase
• Protein Family: Potassium channel
• UniProt Gene Name: AKT1
• UniProt Synonym Gene Names: PKB; RAC; PKB; PKB alpha
• UniProt Entry Name: AKT1_HUMAN

NCBI Description

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]

Uniprot Description

Akt1: an oncogenic AGC kinase that plays a critical role in regulating cell survival and metabolism in many different signaling pathways. Dual phosphorylation is required for its activation. T308 is phosphorylated by PDK1 in the PI3 kinase pathway, and S473 is phosphorylated by mTOR in the mTORC2 pathway. The 'Lys-63'-linked ubiquitination of AKT1 by TRAF6 is important for its translocation to the plasma membrane, phosphorylation, and activation. When Akt is fully phosphorylated it translocates into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its proteosomal degradation. Hyperactive or overexpressed in a number of cancers including breast, prostate, lung, pancreatic, liver, ovarian and colorectal. Over 160 protein substrates are known including many that regulate transcription, metabolism, apoptosis, cell cycle, and growth.

Protein type: Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Oncoprotein; AGC group; AKT family

Chromosomal Location of Human Ortholog: 14q32.32

Cellular Component: cytoplasm; cytosol; microtubule cytoskeleton; nucleoplasm; nucleus; plasma membrane; vesicle

Molecular Function: ATP binding; enzyme binding; identical protein binding; kinase activity; nitric-oxide synthase regulator activity; phosphatidylinositol-3,4,5-triphosphate binding; phosphatidylinositol-3,4-bisphosphate binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; protein serine/threonine/tyrosine kinase activity

Biological Process: activated T cell apoptosis; cell differentiation; cell proliferation; cellular response to insulin stimulus; endocrine pancreas development; G-protein coupled receptor protein signaling pathway; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; insulin receptor signaling pathway; insulin-like growth factor receptor signaling pathway; negative regulation of apoptosis; negative regulation of autophagy; negative regulation of caspase activity; negative regulation of fatty acid beta-oxidation; negative regulation of protein kinase activity; negative regulation of proteolysis; nitric oxide biosynthetic process; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphoinositide-mediated signaling; phosphorylation; platelet activation; positive regulation of blood vessel endothelial cell migration; positive regulation of cell growth; positive regulation of cellular protein metabolic process; positive regulation of endodeoxyribonuclease activity; positive regulation of endothelial cell proliferation; positive regulation of epidermal growth factor receptor signaling pathway; positive regulation of fat cell differentiation; positive regulation of glucose import; positive regulation of glycogen biosynthetic process; positive regulation of lipid biosynthetic process; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of transcription factor activity; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein import into nucleus, translocation; protein modification process; regulation of cell migration; regulation of glycogen biosynthetic process; regulation of mRNA stability; regulation of nitric-oxide synthase activity; regulation of phosphoinositide 3-kinase cascade; response to heat; response to oxidative stress; signal transduction; T cell costimulation

Disease: Breast Cancer; Cowden Syndrome 6; Ovarian Cancer; Proteus Syndrome; Schizophrenia