Essential Role of PKCδ in Apoptosis Induction of Mouse Thymocytes | Science Publications

American Journal of Immunology

A Villunger¹  G. Baier¹  T. Letschka¹  M. Leitges¹  C. Lutz-Nicoladoni¹ 

关键词: Phorbol esters;    PKC isotypes;    thymocytes;    apoptosis induction;   

DOI  :  10.3844/ajisp.2005.14.20

学科分类：过敏症与临床免疫学

来源: Science Publications

【 摘 要 】

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 (PKC, , ) as well as the novel PKCs (, ,  and ), 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 PKC, 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, PKC and PKC, does not significantly affect thymocyte apoptosis. Taken together, we define an essential and non-redundant pro-apoptotic role of PKC in regulating distinct signaling mechanisms that are required to provoke apoptosis of mouse double positive thymocytes in vitro.

【 授权许可】

Unknown