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 Citations (Scopus)

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
Externally publishedYes

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Signal transduction
Protein Kinase C
Signal Transduction
14-3-3 Proteins
Proteins
T-cells
Phorbol Esters
T-Lymphocytes
Chemical activation
ras Proteins
Jurkat Cells
Protein Kinases
Serine
Interleukin-2
Assays
Protein Isoforms
Fusion reactions
Down-Regulation
Cell Line
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hausser, A., Storz, P., Link, G., Stoll, H., Liu, Y. C., Altman, A., ... 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

Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins. / Hausser, Angelika; Storz, Peter; Link, Gisela; Stoll, Hartmut; Liu, Yun Cai; Altman, Amnon; Pfizenmaier, Klaus; Johannes, Franz Josef.

In: Journal of Biological Chemistry, Vol. 274, No. 14, 02.04.1999, p. 9258-9264.

Research output: Contribution to journalArticle

Hausser, A, Storz, P, Link, G, Stoll, H, Liu, YC, Altman, A, Pfizenmaier, K & Johannes, FJ 1999, 'Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins', Journal of Biological Chemistry, vol. 274, no. 14, pp. 9258-9264. https://doi.org/10.1074/jbc.274.14.9258
Hausser, Angelika ; Storz, Peter ; Link, Gisela ; Stoll, Hartmut ; Liu, Yun Cai ; Altman, Amnon ; Pfizenmaier, Klaus ; Johannes, Franz Josef. / Protein kinase C μ is negatively regulated by 14-3-3 signal transduction proteins. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 14. pp. 9258-9264.
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