The PIKK Group
The PIKK group
In eukaryotes, the PIKK (phosphatidyl inositol 3' kinase-related kinases) co-ordinate the cellular response to DNA damage and play critical roles in the control of cell growth, gene expression and V(D)J recombination. Dysfunction of the PIKK leads to clinical manifestations ranging from immunodeficiency to cancer. The PIKKs are a small but essential group of kinases present in all eukaryotes surveyed to date. PIKK members are high molecular mass proteins and of the six members found in mammals, five (ATM, ATR, mTOR, DNA-PK and SMG-1) function as protein serine/threonine kinases.
The molecular target of rapamycin (mTOR), first described as the kinase potently inhibited by the immunosuppressant and antiproliferative agent rapamycin (RAP), is a central modulator of cell growth and a prime strategic target for anti-cancer therapeutic development. mTOR plays a critical role in transducing proliferative signals mediated through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. mTOR does this by activating downstream protein kinases that are required for both ribosomal biosynthesis and translation of key mRNAs of proteins required for promoting the G(1) to S phase transition.
Chiang GG, Abraham RT. (2007) Targeting the mTOR signaling network in cancer. Trends Mol Med. 13 433-42 PMID: 17905659
Abraham RT. (2004) Aug-Sep; PI 3-kinase related kinases: 'big' players in stress-induced signaling pathways. DNA Repair (Amst). 3 883-7 PMID: 15279773
Hiom K. (2005) DNA repair: how to PIKK a partner. Curr Biol. 15 R473-5 PMID: 15964271
Abraham RT, Tibbetts RS. (2005) Cell biology. Guiding ATM to broken DNA. Science. 308 510-1 PMID: 15845843