CELL BIOLOGY AND METABOLISM
Protein Kinase C μ Is Negatively Regulated by 14-3-3 Signal Transduction Proteins*

https://doi.org/10.1074/jbc.274.14.9258Get rights and content
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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.

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This work was supported by Deutsche Forschungsgemeinschaft Grant Jo227/4-2.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.