Par-complex aPKC and Par3 cross-talk with innate immunity NF-κB pathway in epithelial cells

Radia Forteza, Flavia A. Wald, Anastasia Mashukova, Zhanna Kozhekbaeva, Pedro J. Salas

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Components of the Par-complex, atypical PKC and Par3, have been found to be downregulated upon activation of NF-κB in intestinal epithelial cells. To determine their possible role in pro-inflammatory responses we transduced Caco-2 human colon carcinoma cells with constitutively active (ca) PKCι or anti-Par3 shRNA-expressing lentiviral particles. Contrary to previous reports in other cell types, ca-PKCι did not activate, but rather decreased, baseline NF-κB activity in a luminiscence reporter assay. An identical observation applied to a PB1 domain deletion PKCι, which fails to localize to the tight-junction. Conversely, as expected, the same ca-PKCι activated NF-κB in non-polarized HEK293 cells. Likewise, knockdown of Par3 increased NF-κB activity and, surprisingly, greatly enhanced its response to TNFα, as shown by transcription of IL-8, GRO-1, GRO-2 and GRO-3. We conclude that aPKC and Par3 are inhibitors of the canonical NF-κB activation pathway, although perhaps acting through independent pathways, and may be involved in proinflammatory responses.

Original languageEnglish (US)
Pages (from-to)1264-1269
Number of pages6
JournalBiology Open
Volume2
Issue number11
DOIs
StatePublished - Nov 15 2013

Keywords

  • Atypical PKC
  • Epithelial polarity
  • Par-complex

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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