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Defining the combinatorial space of PKC::CARD-CC signal transduction nodes

Jens Staal (UGent) , Yasmine Driege (UGent) , Mira Haegman (UGent) , Marja Kreike (UGent) , Stella Iliaki, Domien Vanneste, Marie Lork, Inna Afonina (UGent) , Harald Braun (UGent) and Rudi Beyaert (UGent)
(2021) FEBS JOURNAL. 288(5). p.1630-1647
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Abstract
Signal transduction typically displays a so-called bow-tie topology: Multiple receptors lead to multiple cellular responses but the signals all pass through a narrow waist of central signaling nodes. One such signaling node for several inflammatory and oncogenic signaling pathways is the CARD-CC/BCL10/MALT1 (CBM) complexes, which get activated by protein kinase C (PKC)-mediated phosphorylation of the caspase activation and recruitment domain (CARD)-coiled-coil domain (CC) component. In humans, there are four CARD-CC family proteins (CARD9, CARD10, CARD11, and CARD14) and 9 true PKC isozymes (alpha to iota). At this moment, less than a handful of PKC::CARD-CC relationships are known. In order to explore the biologically relevant combinatorial space out of all 36 potential permutations in this two-component signaling event, we made use of CARD10-deficient human embryonic kidney 293T cells for subsequent pairwise cotransfections of all CARD-CC family members and all activated PKCs. Upon analysis of NF-kappa B-dependent reporter gene expression, we could define specific PKC::CARD-CC relationships. Surprisingly, as many as 21 PKC::CARD-CC functional combinations were identified. CARD10 was responsive to most PKCs, while CARD14 was mainly activated by PKC delta. The CARD11 activation profile was most similar to that of CARD9. We also discovered the existence of mixed protein complexes between different CARD-CC proteins, which was shown to influence their PKC response profile. Finally, multiple PKCs were found to use a common phosphorylation site to activate CARD9, while additional phosphorylation sites contribute to CARD14 activation. Together, these data reveal the combinatorial space of PKC::CARD-CC signal transduction nodes, which will be valuable for future studies on the regulation of CBM signaling.
Keywords
Cell Biology, Biochemistry, Molecular Biology, MALT1, NF-kappaB, paracaspase, protein kinase C, signal transduction, PROTEIN-KINASE-C, NF-KAPPA-B, COMBINED IMMUNODEFICIENCY, COUPLED RECEPTOR, UBIQUITIN LIGASE, IKK ACTIVATION, MALT1, PKC, MUTATIONS, CARD11

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MLA
Staal, Jens, et al. “Defining the Combinatorial Space of PKC::CARD-CC Signal Transduction Nodes.” FEBS JOURNAL, vol. 288, no. 5, 2021, pp. 1630–47, doi:10.1111/febs.15522.
APA
Staal, J., Driege, Y., Haegman, M., Kreike, M., Iliaki, S., Vanneste, D., … Beyaert, R. (2021). Defining the combinatorial space of PKC::CARD-CC signal transduction nodes. FEBS JOURNAL, 288(5), 1630–1647. https://doi.org/10.1111/febs.15522
Chicago author-date
Staal, Jens, Yasmine Driege, Mira Haegman, Marja Kreike, Stella Iliaki, Domien Vanneste, Marie Lork, Inna Afonina, Harald Braun, and Rudi Beyaert. 2021. “Defining the Combinatorial Space of PKC::CARD-CC Signal Transduction Nodes.” FEBS JOURNAL 288 (5): 1630–47. https://doi.org/10.1111/febs.15522.
Chicago author-date (all authors)
Staal, Jens, Yasmine Driege, Mira Haegman, Marja Kreike, Stella Iliaki, Domien Vanneste, Marie Lork, Inna Afonina, Harald Braun, and Rudi Beyaert. 2021. “Defining the Combinatorial Space of PKC::CARD-CC Signal Transduction Nodes.” FEBS JOURNAL 288 (5): 1630–1647. doi:10.1111/febs.15522.
Vancouver
1.
Staal J, Driege Y, Haegman M, Kreike M, Iliaki S, Vanneste D, et al. Defining the combinatorial space of PKC::CARD-CC signal transduction nodes. FEBS JOURNAL. 2021;288(5):1630–47.
IEEE
[1]
J. Staal et al., “Defining the combinatorial space of PKC::CARD-CC signal transduction nodes,” FEBS JOURNAL, vol. 288, no. 5, pp. 1630–1647, 2021.
@article{8685658,
  abstract     = {{Signal transduction typically displays a so-called bow-tie topology: Multiple receptors lead to multiple cellular responses but the signals all pass through a narrow waist of central signaling nodes. One such signaling node for several inflammatory and oncogenic signaling pathways is the CARD-CC/BCL10/MALT1 (CBM) complexes, which get activated by protein kinase C (PKC)-mediated phosphorylation of the caspase activation and recruitment domain (CARD)-coiled-coil domain (CC) component. In humans, there are four CARD-CC family proteins (CARD9, CARD10, CARD11, and CARD14) and 9 true PKC isozymes (alpha to iota). At this moment, less than a handful of PKC::CARD-CC relationships are known. In order to explore the biologically relevant combinatorial space out of all 36 potential permutations in this two-component signaling event, we made use of CARD10-deficient human embryonic kidney 293T cells for subsequent pairwise cotransfections of all CARD-CC family members and all activated PKCs. Upon analysis of NF-kappa B-dependent reporter gene expression, we could define specific PKC::CARD-CC relationships. Surprisingly, as many as 21 PKC::CARD-CC functional combinations were identified. CARD10 was responsive to most PKCs, while CARD14 was mainly activated by PKC delta. The CARD11 activation profile was most similar to that of CARD9. We also discovered the existence of mixed protein complexes between different CARD-CC proteins, which was shown to influence their PKC response profile. Finally, multiple PKCs were found to use a common phosphorylation site to activate CARD9, while additional phosphorylation sites contribute to CARD14 activation. Together, these data reveal the combinatorial space of PKC::CARD-CC signal transduction nodes, which will be valuable for future studies on the regulation of CBM signaling.}},
  author       = {{Staal, Jens and Driege, Yasmine and Haegman, Mira and Kreike, Marja and Iliaki, Stella and Vanneste, Domien and Lork, Marie and Afonina, Inna and Braun, Harald and Beyaert, Rudi}},
  issn         = {{1742-464X}},
  journal      = {{FEBS JOURNAL}},
  keywords     = {{Cell Biology,Biochemistry,Molecular Biology,MALT1,NF-kappaB,paracaspase,protein kinase C,signal transduction,PROTEIN-KINASE-C,NF-KAPPA-B,COMBINED IMMUNODEFICIENCY,COUPLED RECEPTOR,UBIQUITIN LIGASE,IKK ACTIVATION,MALT1,PKC,MUTATIONS,CARD11}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1630--1647}},
  title        = {{Defining the combinatorial space of PKC::CARD-CC signal transduction nodes}},
  url          = {{http://doi.org/10.1111/febs.15522}},
  volume       = {{288}},
  year         = {{2021}},
}
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