Phosphatidylinositol 3-kinase (PI3K) pathway activation. Tyrosine kinase receptors (TKR) can interact with several PI3K isoforms. RAS proteins can activate PI3Kα and γ isoforms. In addition certain RAS proteins can activate PI3Kδ isoform. G protein-coupled receptors (GPCR) preferentially interact with the PI3Kβ or γ isoforms. Once activated by any of these mechanisms, PI3K interacts with the lipid membrane phosphorylating phosphatidylinositol 4,5-bisphosphate (PIP2) generating phosphatidylinositol 3,4,5-trisphosphate (PIP3). PTEN (phosphatase and tensin homologue deleted on chromosome 10) converts PIP3 into PIP2, regulating the final amount of PIP3 generated. PIP3 triggers a signaling cascade through the activation of AKT, phosphoinositide-dependent protein kinase 1 (PDK1) and their downstream effectors. G = G protein G; p110 = PI3K catalytic subunit; p85 = class IA PI3K regulatory subunit; p87 = class IB PI3K regulatory subunit; p101 = class IB regulatory subunit.