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

Holmgren, Christian LU ; Cornmark, Louise LU ; Kalstad Lønne, Gry LU ; Masoumi, Katarzyna Chmielarska LU and Larsson, Christer LU (2016) In BMC Biochemistry 17(1).
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Co-immunoprecipitation, Protein interaction, Protein kinase C, Smac
in
BMC Biochemistry
volume
17
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85008420032
  • wos:000376360200001
ISSN
1471-2091
DOI
10.1186/s12858-016-0065-x
language
English
LU publication?
yes
id
817ba647-5b98-4dec-b5e2-5f58c040e6cd
date added to LUP
2017-04-21 11:43:01
date last changed
2017-09-18 13:32:49
@article{817ba647-5b98-4dec-b5e2-5f58c040e6cd,
  abstract     = {<p>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.</p>},
  articleno    = {11},
  author       = {Holmgren, Christian and Cornmark, Louise and Kalstad Lønne, Gry and Masoumi, Katarzyna Chmielarska and Larsson, Christer},
  issn         = {1471-2091},
  keyword      = {Co-immunoprecipitation,Protein interaction,Protein kinase C,Smac},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Biochemistry},
  title        = {Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions},
  url          = {http://dx.doi.org/10.1186/s12858-016-0065-x},
  volume       = {17},
  year         = {2016},
}