PTEN, a tumor suppressor important functionally antagonizes PI3K activity T and its intrinsic lipid phosphatase activity t That reduces cellular Re PIP3 pool by converting PIP3 back to PIP2. PTEN was no loss, the cause of the PI3K pathway to cancer as AKT protein kinase B dismissed known, is a serine / SB939 threonine kinase in three isoforms, AKT1, AKT2, AKT3, which are expressed through coded genes PKB, PKB and PKB? is. All three isoforms have a similar structure: a PH Cathedral ne Nterminal, middle serine / threonine catalytic Cathedral ne and a C-terminal regulatory small. AKT activation  of the anchoring of the PH Dom ne of the N-terminal region of AKT PIP3 on the membrane, which then causes a conformational Change of AKT, exposing two residues essential amino acids For phosphorylation16, 17th Both phosphorylation events, T308 and S473 by PDK1 by PDK2, are needed for full gowns’s full activation of AKT 316, 17.
A series of m Resembled PDK2s were identified, including normal ILK PKCbII, ATM and DNA-PK AS-252424 and AKT itself, 15 but it is generally accepted that the main source mTORC2 PDK2 activity T is in most cases Fill 18th Once phosphorylated and activated, phosphorylated AKT many other proteins, for example, and GSK3 Foxos involved thereby regulating a variety of cellular Ren processes in protein synthesis, cell survival, proliferation and metabolism. mTOR mTOR plays an r central role in the regulation of cell growth and proliferation embroidered Lant hrstoffen N availability, cellular Ren energy, oxygen and mitogenic signals. Especially go MTOR rt people to a group of Ser / Thr protein kinase superfamily called PI3K class IV PI3Ks, such as ATM, ATR, DNA-PK and SMG.
mTOR exists in two distinct complexes, mTORC1 and mTORC2. The mTORC1 complex is the catalytic subunit of the protein mTOR, Raptor and PRAS40 mLST8/GbL protein. mTORC2 consists of mTOR, Rictor and mSIN1 mLST8/GbL 21st AKT phosphorylation of mTOR, by TSC2 and PRAS40 time to its inhibitory effect on mTORC1 can be activated to mitigate 22 24th The conclusion of the mTORC1 with the TSC1 and TSC2 tumor suppressors bipartite protein complex has provided a molecular link between mTOR and cancer are available. The best characterized downstream targets of mTORC1 are S6K1 and 4E BP1, both of which are seriously involved in the regulation of protein synthesis. Thus, the activation of mTOR tumor cells with a growth advantage by F Promotion of protein synthesis provide.
When associated with Rictor in mTORC2 complex, mTOR acts as PDK2 to phosphorylate AKT18. The linking of the PI3K pathway to human cancers Although PI3K was two decades ago by its binding characterized activated oncogenes and their connection with cancer in humans has been only in the sp Th 1990s founded RTK when it was shown that the tumor suppressor PTEN as lipid phosphatase PI3 acts. Recent analysis of complete genomic cancer revealed that several components of the PI3K Pathway h Frequently mutated or modified in human cancers 28 33, highlighting the importance of this pathway in cancer therapy.