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. 2022 Jun 5;14(11):2804. doi: 10.3390/cancers14112804

Figure 1.

Figure 1

PI3K/AKT pathway is an intracellular signal transduction pathway that promotes cell growth and proliferation in response to extracellular signals. The binding of the ligands such as growth factors to the receptor tyrosine kinases (RTKs) induces dimerization of two RTK monomers, which consequently leads to activation of the intracellular tyrosine kinase domain and auto-phosphorylation by each monomer. The phosphatidylinositol 3-kinase (PI3K), once activated through direct stimulation of the regulatory subunit bound to the activated receptor, converts phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol 3,4,5-triphosphate (PIP3). PIP3 binds the 3-phosphoinositide-dependent protein kinase-1 (PDK1) at the plasma membrane. PDK1 in turn phosphorylates and activates AKT protein. Once activated, AKT via phosphorylation regulates activation or suppression of several proteins involved in cell growth and proliferation. Phosphatase and tensin homolog (PTEN) is the main downregulation protein that can convert PIP3 into PIP2. Although AKT activation promotes BRCA1 expression through phosphorylation, BRCA1 can downregulate AKT activation by different mechanisms, among which are the activation of protein phosphatase 2A (PP2A), which dephosphorylates AKT.