Direct interaction between protein kinase Cθ (PKCθ) and 14-3-3τ in T cells: 14-3-3 Overexpression results in inhibition of PKCθ translocation and function

Nahum Meller, Yun Cai Liu, Tassie L. Collins, Nathalie Bonnefoy-Bérard, Gottfried Baier, Noah Isakov, Amnon Altman

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Recent studies have documented direct interactions between 14-3-3 proteins and several oncogene and proto-oncogene products involved in signal transduction pathways. Studies on the effects of 14-3-3 proteins on protein kinase C (PKC) activity in vitro have reported conflicting results, and previous attempts to demonstrate a direct association between PKC and 14-3-3 were unsuccessful. Here, we examined potential physical and functional interactions between PKC0, a Ca2+-independent PKC enzyme which is expressed selectively in T lymphocytes, and the 14-3-3τ isoform in vitro and in intact T cells. PKCθ and 14-3-3τ coimmunoprecipitated from Jurkat T cells, and recombinant 14-3-3τ interacted directly with purified PKCθ in vitro. Transient overexpression of 14-3-3τ suppressed stimulation of the interleukin 2 (IL-2) promoter mediated by contransfected wild-type or constitutively active PKCτ, as well as by endogenous PKC in ionomycin- and/or phorbol ester-stimulated cells. This did not represent a general inhibition of activation events, since PKC-independent (but Ca2+-dependent activation of an IL-4 promoter element was not inhibited by 14-3-3τ under similar conditions. Overexpression of wild-type 14-3-3τ also inhibited phorbol ester-induced PKCτ translocation from the cytosol to the membrane in Jurkat cells, while a membrane-targeted form of 14-3-3τ caused increased localization of PKCτ in the particulate fraction in unstimulated cells. Membrane-targeted 14-3-3τ was more effective than wild-type 14-3-3τ in suppressing PKCθ-dependent IL-2 promoter activity, suggesting that 14-3-3τ inhibits the function of PKCθ not only by preventing its translocation to the membrane by also by associating with it. The interaction between 14-3-3 and PKCθ may represent an important general mechanism for regulating PKC- dependent signals and, more specifically, PKCθ-mediated functions during T- cell activation.

Original languageEnglish
Pages (from-to)5782-5791
Number of pages10
JournalMolecular and Cellular Biology
Issue number10
StatePublished - 1 Jan 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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