Among the downstream effectors of PI3Ks (see also section of PI3K/Akt/mTOR signaling), 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1; EC 2.7.11.1) and protein kinase B (PKB)/Akt have a key role in several cancer types. There is evidence that indicates that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer, suggesting that inhibition of PDK1 can inhibit breast cancer progression. PDK1 is the protein kinase responsible for regulating the activity of related kinases in the AGC kinase family (including AKT), by phosphorylating a specific threonine or serine residue within the activation loop (T-loop) which is critical for kinase activation. Many of the kinases activated by PDK1 regulate cellular processes such as cell survival, differentiation, growth, and protein expression, in response to second messenger signals. Activation of PI3K by growth factor signaling results in the production of phosphatidylinositol 3,4-bisphosphate and PIP3, which colocalize AKT and PDK1 to the plasma membrane through interaction with their respective pleckstrin homology (PH) domains, thus allowing PDK1 to phosphorylate AKT in a PIP3-dependent manner. Binding of PIP3 to AKT also induces conformational changes that facilitate PDK1 phosphorylation.