3-Phosphoinositide-dependent protein kinase-1 as an emerging target in the management of breast cancer

Figures & data

Figure 1 Schematic representation of PDK1 structure.

Abbreviations: PDK1, 3-phosphoinositide-dependent protein kinase-1; Thr, threonine; Tyr, tyrosine; Ser, serine.

Figure 2 Activated receptor provides a docking site for PI3K, once bound to the receptor PI3K becomes active and phosphorylates PIP₂, forming PIP₃. PIP₃ acts as a membranous second messenger, providing a docking site for downstream proteins such as Akt and PDK1. Upon binding PIP₃, Akt undergoes a conformational change, facilitating PDK1-dependent phosphorylation of Akt at threonine 308. Once phosphorylated, Akt becomes active and dissociates from the membrane and phosphorylates a variety of downstream targets involved in growth and survival pathways, such as mTOR, MDM2 and BAD. PDK1 is also known to phosphorylate a variety of other downstream proteins, which have also been implicated in cancer cell signaling, such as SGK and YAP. There is also evidence to suggest PI3K-independent PDK1-dependent activation of mTOR.

Abbreviations: PDK1, 3-phosphoinositide-dependent protein kinase-1; PI3K, phosphoinositide-3-kinase; PIP₂, phosphatidylinositol 4,5-bisphosphate; PIP₃, phosphatidylinositol (3,4,5)-trisphosphate; SGK, serum glucocorticoid-dependent kinase; PKC, protein kinase C; YAP, Yes-associated protein kinase; Akt, protein kinase B; mTOR, mammalian target of rapamycin; MDM2, mouse double minute 2 homologue; BAD, Bcl-2-associated death promoter; GSK, glycogen synthase inase.