Protein Phosphorylation
Enrique Pimentel in Handbook of Growth Factors, 2017
The genes of two serine/threonine kinases, Rac-α and Rac-β, have been cloned from human cell lines.489,490 The Rac-α protein is encoded by the AKT1 gene, which is the human homolog of the viral oncogene v-akt. The β form of Rac is a 60-kDa protein that has a carboxyl-terminal extension of 40 amino acids in comparison to the α form. A third human gene, AKT2, closely related to those encoding Rac-α and Rac-β, codes for a 56-kDa protein, Akt-2, which has serine/threonine kinase activity and contains an SH2 domain.491 The AKT2 gene is localized on human chromosome 19, at region 19q.13.1-q13.2 and was found to be amplified in some human ovarian carcinoma cell lines and primary ovarian carcinomas. The Rac/Akt kinases show a high degree of homology to both the protein kinase C and cAMP-dependent families, and may be universally expressed in human cells. These kinases are most probably involved in intracellular signal transduction. The gene encoding another serine/threonine kinase, Mak, is expressed almost exclusively in testicular meiotic cells. The mak gene is not expressed in ovarian cells, including oocytes after the dictyotene stage.492 DNA sequences homologous to the mak gene are highly conserved in mammals and may play an important role in spermatogenesis.
Essential Oils in Cancer Therapy
K. Hüsnü Can Başer, Gerhard Buchbauer in Handbook of Essential Oils, 2020
The EO of Mentha crispa L. (Lamiaceae) and its major constituent rotundifolone and a series of six related monoterpenes were tested for their anticancer effects on the human U87MG glioblastoma cell line (Turkez et al., 2018). Glioblastoma (GBM) is one of the most widespread and aggressive brain tumors. M. crispa EO, 1,2-perillaldehyde epoxide (EPER1), and perillaldehyde (PALD) were more effective than other tested compounds with IC50 values of 16.26, 15.09, and 14.88 μg/mL, respectively. It was also found that the EO increased the expression of BRAF, EGFR (epidermal growth factor receptor), KRAS (kirsten rat sarcoma), NFκB1 (nuclear factor NF-kappa-B), NFκB1A, NFκB2, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase), PIK3R (phosphatidylinositol 3-kinase regulatory), PTEN (phosphatase and tensin homolog), and TP53 (tumor protein p53) genes. Furthermore, the expression of some genes, for example AKT1 (RAC-alpha serine/threonine-protein kinase), AKT2 (RAC-beta serine/threonine-protein kinase), FOS, and RAF1 (proto-oncogene c-RAF) decreased. See Table 14.1.
Exercise Redox Signalling
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
Exercise is one of the best strategies to control glucose blood levels, mostly because of the capacity of contracting muscle to stimulate glucose uptake. Exercise can increase glucose transport to about 50-fold in humans (Katz, 2007). Despite the direct stimulatory effect of exercise-induced ROS on muscle glucose uptake via PI3K (Higaki et al., 2008), other studies showed that Akt2 deficiency did not affect the exercise-stimulated glucose uptake (Sakamoto et al., 2006), supporting the idea that insulin-stimulated glucose uptake pathways might be dissociated from the exercise-stimulated glucose uptake. Several signalling pathways are simultaneously activated following contraction and evoke glucose uptake. Among them, Ca2+/calmodulin-dependent kinase II (CaMKII) and AMPK are the most studied candidates for playing a role in exercise-stimulated glucose uptake (Figure 3.2).
Regulation of dendritic cell function by A20 through high glucose-induced Akt2 signaling
Published in Journal of Receptors and Signal Transduction, 2019
Nguyen Thi Xuan, Nguyen Linh Toan, Can Van Mao, Nguyen Ba Vuong, Nguyen Truong Giang, Nguyen Huy Hoang
This study demonstrates for the first time that the inhibitory effect of A20 expression by high glucose was mediated through insulin/IGF-1/PKB/Akt2 pathway in DCs. Accordingly, treatment of mice with high glucose increased secretion of insulin/IGF1 and reduced A20 release, the effects were blunted in Akt2−/− mice. Upon high glucose exposure on DCs, A20 level was reduced in both control and Akt1-silenced DCs, but not Akt2−/− DCs and down-regulation of A20 was observed in insulin/IGF-1-treated DCs. In consistent, several studies indicated that a loss of A20 protein is frequently found in several cell types upon high glucose [39] or insulin [40] treatment. Clearly, several studies indicated distinct roles of Akt1 and Akt2 in regulating cellular biological properties. A20 expression is down-regulated by NF-κB activation [25], which is mediated through Akt2, but not Akt1 signaling in macrophages [20]. In addition, Akt2 contributes to insulin-mediated regulation of glucose homeostasis [41] and Akt1 attenuates while Akt2 enhances cancer cell migration [42].
Targeting AKT for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2019
Maryam Shariati, Funda Meric-Bernstam
There are three AKT isoforms in humans: AKT1 (PKB-α), AKT2 (PKB-β), and AKT3 (PKB-γ) that share a common structure and a similar activation mechanism [21]. The pleckstrin homology (PH) domain at the N-terminus of AKT interacts with membrane lipids to facilitate AKT recognition and membrane translocation by upstream kinases [22]. The center catalytic region of the protein is the kinase domain, which contains a threonine residue that needs to be phosphorylated for AKT activation [23]. The C-terminal regulatory hydrophobic region of AKT contains a conserved serine residue required for the kinase phosphorylation and activation [24]. All three AKT isoforms share 80% homology in their amino acid sequences with isoform-specific functions [25]. While AKT1 is mainly involved in regulating cell growth and division, AKT2 plays an important role in cellular energy and metabolism [26]. AKT3, the least studied AKT isoform, has been proposed as critical for brain development and the viability of malignant glioma cells [27].
Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Xueqin Huang, Li You, Eugenie Nepovimova, Miroslav Psotka, David Malinak, Marian Valko, Ladislav Sivak, Jan Korabecny, Zbynek Heger, Vojtech Adam, Qinghua Wu, Kamil Kuca
AKT is a class of serine/threonine kinase that belongs to the AGC kinase family, also widely recognised as PKB244. The Akt family consists of three members: Akt1 (PKB α), Akt2 (PKB β), and Akt3 (PKB γ). The three AKT isotypes have similar structures, including the PH domain, the central kinase domain, and the carboxyl-terminal regulatory domain containing hydrophobic motifs245. Although the three subtypes have similar structures, they can perform different functions in cancer and physiology. AKT1, as a growth inducer, promotes tumour cell growth but damages metastasis, while AKT2 can increase tumour cell invasion and metastasis246. Thus, AKT1 is hypothesised to act as an invasion suppressor in the early stages of the disease, while AKT2 promotes invasion in the advanced stages of the disease247. AKT3 is the least studied and has been proven to be closely linked to the progression of triple-negative breast cancer (TNBC)248. The subtype-specific function of AKT remains controversial, and the mechanisms by which it impacts cancer progression require further investigation. Nonetheless, AKT remains a key target for the treatment of cancer.
Related Knowledge Centers
- Enzyme
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- Glycogenesis
- Oncogene
- Protein Kinase B
- Sh2 Domain
- Gluconeogenesis
- Gene
- Insulin Signal Transduction Pathway
- Serine/Threonine-Specific Protein Kinase