Recombinant Human RAC-beta serine/threonine-protein kinase (AKT2)

Function

Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity)

Subcellular Location

Cytoplasm; Nucleus; Cell membrane (Peripheral membrane protein); Early endosome

Disease Association

[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. May play a role in glioblastoma cell survival (PubMed:20167810)] | Type 2 diabetes mellitus (T2D) : A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to 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. [Disease susceptibility is associated with variants affecting the gene represented in this entry] | Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) : 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed. Expressed in myoblasts (PubMed:17565718)

Subunit

Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts (via PH domain) with MTCP1, TCL1A and TCL1B; this interaction may facilitate AKT2 oligomerization and phosphorylation, hence increasing kinase activity (PubMed:10983986). Interacts with PHB2; this interaction may be important for myogenic differentiation (By similarity). Interacts (when phosphorylated) with CLIP3/ClipR-59; this interaction promotes AKT2 recruitment to the plasma membrane (By similarity). Interacts with WDFY2/ProF (via WD repeats 1-3) (PubMed:16792529)

• Jones P.F. et al. Molecular cloning of a second form of rac protein kinase. — Cell Regul. (1991)
• Cheng J.Q. et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. — Proc. Natl. Acad. Sci. U.S.A. (1992)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Grimwood J. et al. The DNA sequence and biology of human chromosome 19. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• PubMed: CI-86AL29TT7EBE3 (AUG-)
• Walker K.S. et al. Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha. — Biochem. J. (1998)
• Laine J. et al. The protooncogene TCL1 is an Akt kinase coactivator. — Mol. Cell (2000)