Skip to main content
. Author manuscript; available in PMC: 2022 Feb 2.
Published in final edited form as: Nat Cancer. 2021 Jun 17;2(6):587–597. doi: 10.1038/s43018-021-00218-4

Figure 1. The PI3K-AKT pathway and the most common PIK3CA mutations in cancer.

Figure 1.

a. The gene expression profile of PI3K isoforms in normal human tissues shown in log2 (TPM+1) scale based on http://gepia.cancer-pku.cn (visited on April 2021). b. Receptor tyrosine kinase (RTK) activation by insulin or growth factors mediates tyrosine phosphorylation which allows the recruitment of the lipid kinase PI3K to the plasma membrane through the p85 regulatory subunit. PI3K phosphorylates the lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). The lipid phosphatase PTEN dephosphorylates PIP3 back to PIP2. PIP3 recruits the serine/threonine kinase AKT to the plasma membrane, where it gets phosphorylated and activated through phosphorylation at T308 by the PDK1 kinase and S473 by mTORC2 kinase complex. AKT then phosphorylates a numerous of substrates promoting glucose, metabolism, cell cycle arrest, cell growth, proliferation, and translation. P denotes protein phosphorylation events. c. The most frequent mutations of the PI3KCA gene by MSK-IMPACT. d. The percentages of the alteration frequency of the PIK3CA gene across human cancers by MSK-IMPACT. Amino-terminal adaptor-binding domain (ABD); Ras-binding domain (RBD); Protein-kinase-C homology-2 (C2).