The PIKK Family of Protein Kinases
- Abstract:
- This chapter provides an overview of the PIKK family with particular emphasis on the human proteins. Six human PIKK family members have been identified to date, and genome scanning suggests that this number is unlikely to increase. Members of the PI3K family play diverse roles in intra cellular signaling triggered by mitogenic and other stimuli through phosphorylating the inositol ring of phosphatidy linositol derivatives, thus generating second messengers for downstream effector pathways. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a crucial role in site-specific V(D)J recombination in the developing immune system and in the non-homologous end-joining (NHEJ) pathway of DNA repair. The protein product of the gene mutated in ataxia-telangiectasia (ATM) and the ATM Rad3-related (ATR) protein have key roles in the signaling of DNA damage. SMG-1, originally identified in a Caenorhabditis elegans screen as a suppressor of morphogen gradient, is involved in the process of nonsense-mediated RNA decay (NMD), while the mammalian target of rapamycin (mTOR; also termed FRAP or RAFT) is involved in controlling cellular growth in response to nutrients and amino acids by playing a pivotal role in controlling the translational machinery. Another member of the PIKK family, TRRAP (transformation/ transcription associated protein), is an essential cofactor for both the c-MYC and the E1A/E2F transcription factor pathways through its interactions with the SAGA and PCAF histone acetyltransferase complexes. It suggests that this class of kinases may directly, or indirectly through partner proteins, be involved in monitoring or modulating of polynucleic acids.