PI 3-kinase related kinases: ‘big’ players in stress-induced signaling pathways

The phosphoinositide 3-kinase related kinases (PIKKs) comprise a family of high molecular mass signaling proteins that play central roles in the control of cell growth, gene expression, and genome surveillance and repair in eukaryotic cells. Mammalian cells express six PIKK family members, five of which—ATM, ATR, mTOR, DNA-PK, and hSMG-1—function as protein serine-threosine kinases. This overview provides some general insights into the pharmacology, biochemistry, and function of this nonconventional group of protein kinases.