December 2010

[JBC] Following PKCδ’s Trail

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Biobits - PKC

The GPCR agonist UTP stimulates the nuclear translocation and activation of PKCδ.

The protein kinase C δ isoform promotes programmed cell death in response to apoptotic stimuli. Typically, PKCδ is activated indirectly through a tyrosine kinase cascade, and then it translocates to the nucleus to induce apoptosis; in some instances, though, PKCδ can be activated directly by phorbol esters, at which point it translocates to the plasma membrane to induce apoptosis. In this article, the researchers developed an approach to visualize the spatial and temporal properties of PKCδ activation using a genetically encoded Förster resonance energy transfer-based reporter specific for this isoform, known as the δ C kinase activity reporter. They observed both mechanisms of activation; phorbol esters triggered fluorescence at the plasma membrane (and also somewhat in the Golgi and mitochondria) in an Src-independent manner, whereas the G-protein-coupled receptor agonist UTP induced activity in the nucleus in an Src-dependent manner. This Src requirement was not solely for translocation but for PKCδ activation as well, as PKCδ pretagged to the nucleus did not activate in the presence of Src inhibitors. This study not only gives new insights into the regulation of PKCδ but also provides a new technological advance for the entire PKC signaling field.

Protein Kinase C δ-Specific Activity Reporter Reveals Agonist-evoked Nuclear Activity Controlled by Src Family of Kinases

Taketoshi Kajimoto, Seishiro Sawamura, Yumi Tohyama, Yasuo Mori and Alexandra C. Newton

J. Biol. Chem., published online Oct. 19, 2010


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