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The Role of Myristoylated Protein Kinase C Substrates in Intracellular Signaling Pathways in Macrophages

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Macrophage Biology and Activation

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 181))

Abstract

The protein kinases C (PKC) are a family of diacylglycerol-activated, calcium-dependent protein kinases that regulate diverse cellular pathways in macrophages, including those leading to phagocytosis and the secretion of ara-chidonic acid metabolites and reactive oxygen intermediates (Kikkawa et al. 1989; Aderem 1988; Clark 1990). Very little is known about the molecular mechanism by which PKC mediates such diverse responses. It is known, however, that PKC-mediated events in macrophages are profoundly influenced by inflammatory mediators such as bacterial lipopolysaccharide (LPS) and by cytokines such as gamma-interferon (IFN-γ) and tumor necrosis factor (TNF-α) (Hamilton and Adams 1987). Thus, while LPS alone is incapable of activating PKC, it can prime macrophages for vastly increased PKC-dependent responses such as the release of eicosanoids and prostanoids (Aderem et al. 1986a, Aderem and Cohn 1988). Concomitant with priming, LPS also induces the transcription, translation, and myristoylation of three macrophage proteins with apparent molecular masses of 40, 42, and 68 kDa (Aderem et al. 1986b, 1988a). All three proteins are substrates for PKC and are therefore excellent candidate effectors of PKC-induced responses. In addition, we have characterized a 48-kDa myristoylated PKC substrate which is induced in macrophages by IFN-γ and which appears likely to mediate some of the responses of this macrophage-activating cytokine (Aderem et al. 1988b).

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  1. The Rockefeller University, 1230 York Avenue, New York, NY, 10021, USA

    A. Aderem

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  1. University of Kansas Cancer Ctr., Kansas City, KA, 66160-7312, USA

    Stephen W. Russell (Wilkinson Distinguished Professor and Director) (Wilkinson Distinguished Professor and Director)

  2. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Siamon Gordon

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Aderem, A. (1992). The Role of Myristoylated Protein Kinase C Substrates in Intracellular Signaling Pathways in Macrophages. In: Russell, S.W., Gordon, S. (eds) Macrophage Biology and Activation. Current Topics in Microbiology and Immunology, vol 181. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77377-8_7

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  • DOI: https://doi.org/10.1007/978-3-642-77377-8_7

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