Showing papers by "Denise R. Cooper published in 2006"
TL;DR: A clear case will be made to show that these isoforms are not only expressed but are importantly involved in regulation of insulin metabolic effects, in the conventional and novel categories.
96 citations
TL;DR: The results indicate that RA regulates the expression of PKCδ alternative splicing variants in NT2 cells, and it is suggested that the molecular mechanisms regulating differentiation and apoptosis could be understood by alternative expression ofPKC δ isoforms.
Abstract: NT2 cells are a human teratocarcinoma cell line that, upon treatment with retinoic acid (RA), begin differentiating into a neuronal phenotype. The transformation of undifferentiated NT2 cells into hNT neurons presents an opportunity to investigate the mechanisms involved in neurogenesis because a key component is cell apoptosis, which is essential for building neural networks. Protein kinase Cδ (PKCδ) plays an important role as a mediator of cellular apoptosis in response to various stimuli. PKCδ (δI) is proteolytically cleaved at its hinge region (V3) by caspase 3 and the catalytic fragment is sufficient to induce apoptosis in various cell types. Mouse PKCδII is rendered caspase resistant due to an insertion of 78 bp within the caspase recognition site in its V3 domain. No functional role has been attributed to these alternatively spliced variants of PKCδ. We sought to find a correlation between the onset of apoptosis, neurogenesis, and the expression of PKCδ isoforms. Our results indicate that RA regulates the expression of PKCδ alternative splicing variants in NT2 cells. Further, overexpression of PKCδI promotes apoptosis while PKCδII overexpression shields the cells from apoptosis. This is the first report to attribute physiological function to PKCδI and -δII isoforms. Next we demonstrated that mouse embryonic stem cells differentiate in vitro into dopaminergic neurons upon stimulation with RA and ciliary neurotrophic factor. These cells showed a simultaneous increase in tyrosine hydroxylase and PKCδII expression. We suggest that the molecular mechanisms regulating differentiation and apoptosis could be understood by alternative expression of PKCδ isoforms.
40 citations
TL;DR: This study indicates that the expression of PKCdelta may be regulated in a rapid manner during the course of insulin action in skeletal muscle and raises the possibility that PKCcd delta may be an immediate early response gene activated by insulin.
17 citations