De novo purine biosynthesis and PDK1-associated signaling pathways.

<p>(A) Biosynthesis of inosine monophosphate (IMP) from phosphoribosyl pyrophosphate (PRPP) is catalyzed by six enzymes and their assemblies. A 3-enzyme core assembly (blue box) catalyzes the first half of the pathway while the purinosome (red box) regulates the entire pathway. (B) 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is recruited to the plasma membrane upon activation of phosphoinositide 3-kinase (PI3K). Subsequently, PI3K and PDK1 activate Akt for various signaling cascades, including the mammalian target of rapamycin (mTOR). Alternatively, cytoplasmic PDK1 phosphorylates several kinases, including protein kinase C (PKC) and p70 ribosomal protein S6 kinase (S6K), in an Akt-independent manner. Pharmacological inhibitors used in this work are also indicated.