Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions

Christian Holmgren, Louise Cornmark, Gry Kalstad Lønne, Katarzyna Chmielarska Masoumi, Christer Larsson

Research output: Contribution to journalArticlepeer-review


Background: Protein kinase C o (PKCo) is known to be an important regulator of apoptosis, having mainly pro-but also anti-Apoptotic effects depending on context. In a previous study, we found that PKCo interacts with the pro-Apoptotic protein Smac. Smac facilitates apoptosis by suppressing inhibitor of apoptosis proteins (IAPs). We previously established that the PKCo-Smac complex dissociates during induction of apoptosis indicating a functional importance. Because the knowledge on the molecular determinants of the interaction is limited, we aimed at characterizing the interactions between PKCo and Smac. Results: We found that PKCo binds directly to Smac through its regulatory domain. The interaction is enhanced by the PKC activator TPA and seems to be independent of PKCo catalytic activity since the PKC kinase inhibitor GF109203X did not inhibit the interaction. In addition, we found that C1 and C2 domains from several PKC isoforms have Smac-binding capacity. Conclusions: Our data demonstrate that the Smac-PKCo interaction is direct and that it is facilitated by an open conformation of PKCo. The binding is mediated via the PKCo regulatory domain and both the C1 and C2 domains have Smac-binding capacity. With this study we thereby provide molecular information on an interaction between two apoptosis-regulating proteins.

Original languageEnglish
Article number11
JournalBMC Biochemistry
Issue number1
Publication statusPublished - 2016

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology
  • Cell and Molecular Biology

Free keywords

  • Co-immunoprecipitation
  • Protein interaction
  • Protein kinase C
  • Smac


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