TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in glioma cells and glioma stem cells in vitro and in vivo.

Glioblastomas (GBM) are characterized by resistance to chemotherapy and radiotherapy, and therefore, alternative therapeutic approaches are needed. TRAIL induces apoptosis in cancer but not in normal cells and is considered to be a promising anti-tumor agent. However, its short in vivo half-life and lack of efficient administration modes are serious impediments to its therapeutic efficacy.

The regulatory domain of protein kinase C delta positively regulates insulin receptor signaling.

Protein kinase C delta (PKCdelta) is induced by insulin to rapidly associate with insulin receptor (IR) and upregulates insulin signaling. We utilized specific JM and CT receptor domains and chimeras of PKCalpha and PKCdelta regulatory and catalytic domains to elucidate which components of PKCdelta are responsible for positive regulatory effects of PKCdelta on IR signaling. Studies were performed on L6 and L8 skeletal muscle myoblasts and myotubes.

Phosphorylation of protein kinase Cdelta on distinct tyrosine residues induces sustained activation of Erk1/2 via down-regulation of MKP-1: role in the apoptotic effect of etoposide.

The mechanism underlying the important role of protein kinase Cdelta (PKCdelta) in the apoptotic effect of etoposide in glioma cells is incompletely understood. Here, we examined the role of PKCdelta in the activation of Erk1/2 by etoposide. We found that etoposide induced persistent activation of Erk1/2 and nuclear translocation of phospho-Erk1/2.

The localization of protein kinase Cdelta in different subcellular sites affects its proapoptotic and antiapoptotic functions and the activation of distinct downstream signaling pathways.

Protein kinase Cdelta (PKCdelta) regulates cell apoptosis and survival in diverse cellular systems. PKCdelta translocates to different subcellular sites in response to apoptotic stimuli; however, the role of its subcellular localization in its proapoptotic and antiapoptotic functions is just beginning to be understood. Here, we used a PKCdelta constitutively active mutant targeted to the cytosol, nucleus, mitochondria, and endoplasmic reticulum (ER) and examined whether the subcellular localization of PKCdelta affects its apoptotic and survival functions.

Tyrosine 311 is phosphorylated by c-Abl and promotes the apoptotic effect of PKCdelta in glioma cells.

In this study we characterized the phosphorylation of tyrosine 311 and its role in the apoptotic function of PKCdelta in glioma cells. We found that c-Abl phosphorylated PKCdelta on tyrosine 311 in response to H2O2 and that this phosphorylation contributed to the apoptotic effect of H2O2. In contrast, Src, Lyn, and Yes were not involved in the phosphorylation of tyrosine 311 by H2O2.

PKCepsilon induces astrocytic differentiation of multipotential neural precursor cells.

In this study, we examined the role of PKC in the differentiation of multipotential neural precursor cells (NPCs). We found that the NPCs expressed PKCalpha,beta2,delta,epsilon,zeta and low levels of PKCgamma. The PKC activator, PMA, selectively increased the number of astrocytes, whereas it decreased the generation of neurons and oligodendrocytes.

Protein kinase C-epsilon regulates the apoptosis and survival of glioma cells.

In this study, we examined the role of protein kinase C (PKC)-epsilon in the apoptosis and survival of glioma cells using tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of PKCepsilon expression. Treatment of glioma cells with TRAIL induced activation, caspase-dependent cleavage, and down-regulation of PKCepsilon within 3 to 5 hours of treatment. Overexpression of PKCepsilon inhibited the apoptosis induced by TRAIL, acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c release from the mitochondria.

Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis.

Protein kinase Cdelta (PKCdelta) regulates cell apoptosis in a cell- and stimulus-specific manner. Here, we studied the role of PKCdelta in the apoptotic effect of TRAIL in glioma cells. We found that transfection of the cells with a PKCdelta kinase-dead mutant (K376R) or with a small interfering RNA targeting the PKCdelta mRNA increased the apoptotic effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), whereas overexpression of PKCdelta decreased it.