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The PI3K-Akt pathway is a survival pathway that regulates cell proliferation, differentiation, apoptosis, and migration. The upstream stimulators of the pathway include multiple growth hormones, cytokines, and foreign molecules. The PI3K-Akt pathway has been shown to play crucial roles in the physiology and pathophysiology of many types of cells. Abnormal increase or decrease in the PI3K-Akt pathway activity is associated with a number of diseases such as diabetes, laminopathy, cancer, stroke, and neurodegenerative diseases and manipulation of the pathway has been proposed for the treatment of these diseases. The PI3K-Akt also plays an important role in regulating neuronal function via protein ataxin-1, GABA receptor, and disruption of the pathway is associated with diseases such as Huntingtin disease.
The key enzyme of the pathway, PI3K, converts phosphatidylinositol 4, 5-biphosphate into phosphatidylinositol 3, 4, 5-triphosphate, which binds both Akt and 3-phosphoinositide-dependent protein kinase 1 (PDK1), allowing PDK1 to phosphorylate Akt. Class 1A PI3K is composed of two subunits: the catalytic subunit p110 and the regulatory subunit p85. There are four isoforms of p110: p110-α, β, γ, δ and three p85 isoforms: p85-alpha, beta, and gamma. AKT is one of the major downstream effectors of PI3K, and it was originally identified as a critical component of the insulin receptor intracellular signaling. Upon PI3K activation, AKT is translocated through its PH domain to the inner membrane, where it is phosphorylated by PDK1 on its activation loop (T308). This AKT modification is sufficient to activate the mammalian target of rapamycin complex 1 (mTORC1) by the direct phosphorylation and activation of the proline-rich AKT substrate of 40 kDa (PRAS40) and the tuberous sclerosis protein 2 (TSC2).
Figure 1. The PI3K-AKT signaling pathway.
Since PI3K-AKT axis has been classified among the most frequently activated pathways in cancer, members of the cascade represent an attractive target for cancer therapeutics. A number of molecules targeting members of the PI3K axis have been developed and evaluated in preclinical studies as well as in clinical trials. These targeted drugs include isoform-specific (p110 α , p110 β , p110 γ , p110 δ ) or mTOR inhibitors, pan-class I PI3K inhibitors, dual PI3K/mTOR inhibitors, and AKT inhibitors, which are all currently in clinical development.
Alteration of the PI3K-AKT pathway is strongly implicated in cancer pathogenesis, and targeting the effectors of this pathway is a promising therapeutic approach. The growing interest in developing PI3K inhibitors clearly suggests the central role of PI3Ks in cancer treatment. Creative Biogene is able to offer a variety of PI3K-AKT signaling pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.
PI3K-AKT Signaling Pathway Product Panel
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