Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins

Angelika Hausser, Peter Storz, Gisela Link, Hartmut Stoll, Yun Cai Liu, Amnon Altman, Klaus Pfizenmaier, Franz Josef Johannes

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Recent studies have documented direct interaction between 14-3-3 proteins and key molecules in signal transduction pathways like Ras, Cbl, and protein kinases. In T cells, the 14-3-3τ isoform has been shown to associate with protein kinase C θ and to negatively regulate interleukin-2 secretion. Here we present data that 14-3-3τ interacts with protein kinase C μ (PKCμ), a subtype that differs from other PKC members in structure and activation mechanisms. Specific interaction of PKCμ and 14-3-3τ can be shown in the T cell line Jurkat by immunocoprecipitiation and by pulldown assays of either endogenous or overexpressed proteins using PKCμ-specific antibodies and GST-14-3-3 fusion proteins, respectively. Using PKCμ deletion mutants, the 14-3-3τ binding region is mapped within the regulatory C1 domain. Binding of 14-3-3τ to PKCμ is significantly enhanced upon phorbol ester stimulation of PKCμ kinase activity in Jurkat cells and occurs via a Cbl-like serine containing consensus motif. However, 14-3-3τ is not a substrate of PKCμ. In contrast 14-3-3τ strongly down-regulates PKCμ kinase activity in vitro. Moreover, overexpression of 14-3-3τ significantly reduced phorbol ester induced activation of PKCμ kinase activity in intact cells. We therefore conclude that 14-3-3τ is a negative regulator of PKCμ in T cells.

Original languageEnglish (US)
Pages (from-to)9258-9264
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number14
DOIs
StatePublished - Apr 2 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hausser, A., Storz, P., Link, G., Stoll, H., Liu, Y. C., Altman, A., Pfizenmaier, K., & Johannes, F. J. (1999). Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins. Journal of Biological Chemistry, 274(14), 9258-9264. https://doi.org/10.1074/jbc.274.14.9258