protein

AKT2, Unactive recombinant protein

MBS515354

0.02 mg

270 USD

Recombinant Protein

AKT2, Unactive recombinant protein

[AKT2]

[PRKBB; PKBBETA; RAC-BETA]

[Homo sapiens v-akt murine thymoma viral oncogene homolog 2 (AKT2), transcript variant 1, mRNA; RAC-beta serine/threonine-protein kinase; RAC-beta serine/threonine-protein kinase; PKB beta; RAC-PK-beta; protein kinase Akt-2; protein kinase B beta; rac protein kinase beta; murine thymoma viral (v-akt) homolog-2; v-akt murine thymoma viral oncogene homolog 2; Protein kinase Akt-2; Protein kinase B beta; PKB beta; RAC-PK-beta]

[AKT2]

[PRKBB; PKBBETA; RAC-BETA]

[AKT2; AKT2; PKBB; PRKBB; HIHGHH; PKBBETA; RAC-BETA; PKB beta]

AKT2_HUMAN

Sf9 insect cells

5317

>90%

Recombinant protein stored in 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol

0.2 ug/ml

Store product at -70 degree C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles. Shipping: Ships on dry ice.

Kinase Assay, Western Blot (WB)

SDS-PAGE

Unactive Kinase; Signaling Proteins - Unactive Kinases

Recombinant full-length human AKT2 was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. Scientific Background: AKT2 or Protein Kinase B beta (PKBbeta) is a serine/threonine kinase that is a member of the AKT family. AKT2 like the other AKT members is activated in cells in response to diverse stimuli such as hormones, growth factors and extracellular matrix components and is involved in glucose metabolism, transcription, survival, cell proliferation, angiogenesis, and cell motility (1). The PI3K generates phosphatidylinositol-3, 4, 5-trisphosphate (PIP3), a lipid second messenger essential for the translocation of AKT2 to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase-1 (PDK-1) (2).

1.Coffer, PJ. et al: Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J. 1998 Oct 1; 335 (Pt 1):1-13. 2.Anderson, KE. et al: Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr Biol. 1998 Jun 4;8(12): 684-91.

339895851

NP_001617.1

NM_001626

P31751

~85 kDa

AKT Phosphorylates Targets In The Cytosol Pathway (106475); AKT Phosphorylates Targets In The Nucleus Pathway (106476); AKT-mediated Inactivation Of FOXO1A Pathway (106333); AMPK Signaling Pathway (198868); Activation Of BAD And Translocation To Mitochondria Pathway (105659); Activation Of BH3-only Proteins Pathway (105658); Activation Of PKB Pathway (106436); Acute Myeloid Leukemia Pathway (83117); Acute Myeloid Leukemia Pathway (529); Adaptive Immune System Pathway (366160)

This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains. The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. The encoded protein is a general protein kinase capable of phophorylating several known proteins. [provided by RefSeq, Jul 2008]

Function: AKT2 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. Ref.10One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'. Ref.10. Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Enzyme regulation: Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation. Aminofurazans are potent AKT2 inhibitors. Ref.24 Ref.25. Subunit structure: Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CLK2, PBH2 and TRAF6. Ref.7 Ref.10 Ref.14. Subcellular location: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note: Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2. Ref.10. Tissue specificity: Expressed in all cell types so far analyzed. Domain: Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. Post-translational modification: Phosphorylation on Thr-309 and Ser-474 is required for full activity.Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Ref.6 Ref.8 Ref.12 Ref.20O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1 . By similarity. Involvement in disease: Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. With AKT3, plays also a pivotal role in the biology of glioblastoma.Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.28Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) [MIM:240900]: A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29. Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.Contains 1 AGC-kinase C-terminal domain.Contains 1 PH domain.Contains 1 protein kinase domain. Caution: In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain. Biophysicochemical propertiesKinetic parameters:KM=358.4 uM for ATP (for purified and in vitro activated AKT2) Ref.9KM=3.4 uM for peptide substrate (for purified and in vitro activated AKT2)KM=564 uM for ATP (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)KM=2.3 uM for peptide substrate (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)

0.02 mg

270 USD

0.05 mg

450