Protein kinase Cs (PKCs) are activated by antigen receptors in lymphocytes, but little is known about proximal targets for PKCs in antigen receptor–mediated responses. In this report, we define a role for diacylglycerol-regulated PKC isoforms in controlling the activity of the serine/ threonine kinase protein kinase D (PKD; also known as PKC m ) in T cells, B cells, and mast cells. Antigen rece...

The pathogenesis of Alzheimer's disease (AD), characterized by prevalent neuronal death and extracellular deposit of amyloid plaques, is poorly understood. DNA lesions downstream of reduced DNA repair ability have been reported in AD brains. Neurons predominantly use a mechanism to repair double-strand DNA breaks (DSB), which is non-homologous end joining (NHEJ). NHEJ requires DNA-dependent pro...

Understanding the molecular details associated with aberrant high mobility group A2 (HMGA2) gene expression is key to establishing the mechanism(s) underlying its oncogenic potential and effect on the development of therapeutic strategies. Here, we report the involvement of HMGA2 in impairing DNA-dependent protein kinase (DNA-PK) during the nonhomologous end joining (NHEJ) process. We showed th...

DNA-dependent protein kinase (DNA-PK) consists of a 460 kDa subunit that contains the catalytic domain (DNA-PKcs) complexed with two polypeptides of 70 kDa and 80 kDa (Ku70 and Ku80) which comprise the Ku autoantigen. DNA-PKcs requires association with DNA via Ku for catalytic activation and is implicated in double strand break repair, V(D)J recombination and transcription. We have utilised a c...

DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes rep...

The family of protein kinases C (PKCs) has been implicated in signal transmission leading to apoptosis induction and/or survival. These effects are cell type and tissue dependent. Numerous studies employing phorbol ester, a pleiotropic PKC activator, strongly implicated PKC in apoptosis induction of thymocytes. However, phorbol esters activate both, the conventional PKCs (PKCα, β, γ) as well as...

Recent studies have shown that recombinant adeno-associated virus (rAAV) can persist in episomal form; however, factors affecting rAAV persistence are poorly understood. DNA-dependent PK (DNA-PK) is a DNA repair enzyme, which we previously found played an important role in determining the molecular fate of the rAAV genome in mouse skeletal muscle. In the present study, we tested the effect of D...

Protein kinase Cs (PKCs) are activated by antigen receptors in lymphocytes, but little is known about proximal targets for PKCs in antigen receptor-mediated responses. In this report, we define a role for diacylglycerol-regulated PKC isoforms in controlling the activity of the serine/threonine kinase protein kinase D (PKD; also known as PKC mu) in T cells, B cells, and mast cells. Antigen recep...

Deoxyribonucleic acid double-stranded breaks act as intermediates in Ig V(D)J recombination and probably perform a similar function in class switch recombination between IgH C genes. In SCID mice, V(D)J recombination is blocked because the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) protein is defective. We show in this study that switching to all isotypes examined was detectable ...

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG) stimulate innate immune responses. Phosphoinositide 3-kinase (PI3K) has been implicated in CpG-induced immune activation; however, its precise role has not yet been clarified. CpG-induced production of IL-10 was dramatically increased in macrophages deficient in PI3Kγ (p110γ(-/-)). By contrast, LPS-induced production of IL...