PI3K is an intracellular phosphatidylinositol kinase, with v. Src and v. The product of an oncogene such as ras is involved, and PI3K itself has a serine/threonine (Ser/Thr) kinase activity and also has phosphatidylinositol kinase activity. It consists of a regulatory subunit p85 and a catalytic subunit p1 10. Activation and inhibition of PDK.

PI3K itself has a serine/threonine (Ser/Thr) kinase activity and also has phosphatidylinositol kinase activity. PI3K can be divided into three categories, with different structures and functions. The most widely studied of these is the class I PI3K, which is a heterodimer composed of a regulatory subunit and a catalytic subunit. The regulatory subunit contains the SH2 and SH3 domains and interacts with a target protein containing the corresponding binding site. This subunit is commonly referred to as p85, with reference to the first isotype found. There are four kinds of catalytic subunits, namely, p110α, β, δ, γ, while δ, γ are limited to white blood cells, and the rest are widely distributed in various cells. It consists of a regulatory subunit p85 and a catalytic subunit p110.

Activation and inhibition
Upon receipt of a signal from a tyrosine kinase and a G protein-coupled receptor, the p85 regulatory subunit of PI3K is recruited to the site adjacent to the plasma membrane, and the p110 subunit binds the substrate Ptd Ins by binding to the p85 subunit (4). 5) P2 (PIP2, phosphatidylinositol 2 phosphate) is converted to Ptd Ins (3, 4, 5) P3 (PIP3, phosphatidylinositol 3 phosphate). PI (3,4,5) P3 binds to the N-terminal PH domain of protein kinase B (PKB, Akt). Transfer Akt from the cytoplasm to the cell membrane. And with the help of inositol 3-phosphate-associated protein kinase 1 (PDKI) and inositol 3-phosphate-dependent protein kinase 2 (PDK2), respectively, the threonine phosphorylation site (Thr308) on Akt protein and The serine phosphorylation site (Ser473) is phosphorylated to activate it.

Activated Akt activates its substrate rapamycin target protein (mTOR) by direct and indirect pathways: direct phosphorylation of mTOR, or maintenance of Rheb GTP by inactivating tuberous sclerosis complex 2 (TSC2) Binding states then enhance mTOR activation. The product encoded by the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) can dephosphorylate PIP3 to form PIP2 at position D3, thereby realizing PI3K/Akt signal. Negative regulation of the pathway inhibits cell proliferation and promotes apoptosis.

As a protooncogene, the serine/threonine kinase Akt (also known as protein kinase B or PKB) has become a major concern in the medical field because it regulates various cellular functions (including metabolism, growth, It plays an important role in proliferation, survival, transcription, and protein synthesis. Factors that activate the Akt signaling cascade, including receptor tyrosine kinases, integrins, B-cell and T-cell receptors, cytokine receptors, G-protein coupled receptors, and others capable of passing phosphatidylinositol III Kinase (PI3K) induces stimulation of triphosphate (3,4,5) phosphatidylinositol (PIP3) production. These lipids serve as docking sites for protein membranes with a Pleek substrate protein homology (PH) domain, including Akt and its upstream activator PDK1. PDK1 on the membrane phosphorylates it at the threonine 308 site of AKt, resulting in partial activation of Akt. The serine 473 site is phosphorylated by mTORC2 and stimulates the complete enzymatic activity of Akt. Members of the PI3K-associated kinase (PIKK) family, including DNA-PK, also phosphorylate at the Akt serine 473 site. Akt can be dephosphorylated by protein phosphatase 2A (PP2A) and the PH-domain-rich leucine-repetitive-containing protein phosphatase (PHLPP1/2). In addition, the tumor suppressor gene phosphatase and the tensin homolog protein (PTEN) also inhibit Akt activity by dephosphorylation of PIP3.

AKT is a class of AGC family serine/threonine kinases that have three major domains: the PH domain (affinity to PIP3 and therefore essential for binding to the membrane); catalytic domain; regulatory domain. Thr308 and Ser473 are located on the latter two domains, respectively, and the PH and catalytic domains are relatively conserved among different Akt isoforms. There are three major isoforms of AKT in mammals: Aktl, 2, 3. Akt1 is widely expressed in tissues, and Akt2 is mainly expressed in muscle and fat cells. Akt3 is mainly expressed in the testis and brain. With the deepening of the research, a truncated variant of Aktl3-(γ1) in the hydrophobic domain was also found. Akt phosphorylation substrate is numerous, but generally phosphorylation of the substrate (silk/su There is a conserved motif sequence near the amino acid, S/T) site: RXRXXS*/T*, where R represents arginine and X represents any amino acid. Based on this conservation, the use of such Motif antibodies has been instrumental in the systematic study of Akt downstream signaling pathways.

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