Defining the combinatorial space of PKC:CARD‐CC signal transduction nodes. (1st September 2020)
- Record Type:
- Journal Article
- Title:
- Defining the combinatorial space of PKC:CARD‐CC signal transduction nodes. (1st September 2020)
- Main Title:
- Defining the combinatorial space of PKC::CARD‐CC signal transduction nodes
- Authors:
- Staal, Jens
Driege, Yasmine
Haegman, Mira
Kreike, Marja
Iliaki, Styliani
Vanneste, Domien
Lork, Marie
Afonina, Inna S.
Braun, Harald
Beyaert, Rudi - Abstract:
- 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 (α to ι). 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‐κB‐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 PKCδ. 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,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 (α to ι). 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‐κB‐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 PKCδ. 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. Abstract : CARD‐CC/BCL10/MALT1 signaling complexes are activated by PKC‐mediated phosphorylation in response to specific upstream signals, leading to NF‐κB‐dependent gene expression. The caspase activation and recruitment domain (CARD)‐coiled‐coil domain (CC) family consists of four members and the PKC family of 9 members (subdivided in conventional, novel, and atypical subclasses). Here, we investigate the possible functional interactions between each specific PKC and CARD‐CC family member. … (more)
- Is Part Of:
- FEBS journal. Volume 288:Number 5(2021)
- Journal:
- FEBS journal
- Issue:
- Volume 288:Number 5(2021)
- Issue Display:
- Volume 288, Issue 5 (2021)
- Year:
- 2021
- Volume:
- 288
- Issue:
- 5
- Issue Sort Value:
- 2021-0288-0005-0000
- Page Start:
- 1630
- Page End:
- 1647
- Publication Date:
- 2020-09-01
- Subjects:
- MALT1 -- NF‐kappaB -- paracaspase -- protein kinase C -- signal transduction
Biochemistry -- Periodicals
Molecular biology -- Periodicals
Pathology, Molecular -- Periodicals
572 - Journal URLs:
- http://firstsearch.oclc.org ↗
http://gateway.ovid.com/ovidweb.cgi?T=JS&MODE=ovid&NEWS=n&PAGE=toc&D=ovft&AN=01038983-000000000-00000 ↗
http://www.blackwell-synergy.com/servlet/useragent?func=showIssues&code=ejb ↗
http://onlinelibrary.wiley.com/ ↗
http://www.blackwell-synergy.com/servlet/useragent?func=showIssues&code=ejb ↗ - DOI:
- 10.1111/febs.15522 ↗
- Languages:
- English
- ISSNs:
- 1742-464X
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 3901.578500
British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 15869.xml