Fig. 1
From: Targeting PI3K/Akt signal transduction for cancer therapy
Upstream activation of the PI3K/Akt signaling pathway. On the one hand, ligands combined with specific RTKs (EGFR, VEGFR and FGFR) can activate class I PI3Ks via RAS; on the other hand, class I PI3Ks can be activated by BCRs through B cell adapters and by GPCRs. The FGFR substrate FRS2 is phosphorylated in combination with GRB2, SOS and GAB1 to activate class I PI3Ks. In addition to being activated by EGFR, class II PI3Ks can be activated by TCRs. While class III PI3Ks are activated by amino acids, total activated PI3K phosphorylates the third carbon of the PIP2 inositol head and transforms it into PIP3 to thereby activate AKT via PDK1 and RAC, and this transformation process can be inhibited by PTEN. In addition, IGF-1 in combination with IGF1R can recruit IRS-1 and class I PI3Ks and then participate in the conversion of PIP2 to PIP3. Moreover, mTORC2 can affect the activity of Akt by affecting the phosphorylation of Akt and then affect downstream mTORC1 via TSC1/2, and both Akt and mTORC1 can be activated by TBK1. Moreover, TRAF6 can affect the activity of Akt by affecting its ubiquitylation. Furthermore, DNA damage can affect Akt via ATM and ATR
