Essential Role of PKCδ in Apoptosis Induction of Mouse Thymocytes
- 1 Innsbruck Medical University, Australia
- 2 Medical University, Australia
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 the novel PKCs (δ, ε, η and θ), the PKC isotype(s) selectively involved in this process have not been established. In this study we used selective pharmacological PKC inhibitors and our established set of PKC knockout mice to define the PKC isotype that is involved in cell death induction of thymocytes. Pharmacological inhibition of nPKCs and in particular gene ablation of PKCδ, results in a profound reduction of p53-dependent as well as independent apoptosis induction. In strict contrast, loss of conventional PKCs as well as loss of two other thymocyte-expressed nPKC family members, PKCε and PKCθ, does not significantly affect thymocyte apoptosis. Taken together, we define an essential and non-redundant pro-apoptotic role of PKCδ in regulating distinct signaling mechanisms that are required to provoke apoptosis of mouse double positive thymocytes in vitro.
Copyright: © 2005 C. Lutz-Nicoladoni, T. Letschka, M. Leitges, A Villunger and G. Baier. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- 2,542 Views
- 1,978 Downloads
- 2 Citations
- Phorbol esters
- PKC isotypes
- apoptosis induction