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PI3K and AKT at the Interface of Signaling and Metabolism

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PI3K and AKT Isoforms in Immunity

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 436))

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Abstract

The PI3K/AKT signaling module is recruited by several receptors implicated in maintaining tissue and metabolic homeostasis and signaling pathways controlling immune responses. Constitutive activation of PI3K/AKT signaling leads to tissue overgrowth and is frequently observed in cancer cells, whereas reduced PI3K/AKT signaling is associated with diabetes and growth defects. Thus, a critical roadblock to effective PI3K-targeted therapy comes from the crucial role of PI3K/AKT signaling in systemic metabolic homeostasis. This chapter describes the role of PI3K/AKT in insulin signaling and metabolic homeostasis and the interplay between insulin action and metabolic feedback loops that cause resistance to PI3K-targeted therapies. Furthermore, we provide examples of insulin-independent roles for PI3K/AKT in metabolic homeostasis, and some generalizations on the action of PI3K/AKT signaling at the interface of signaling and metabolism are derived. Finally, the specific roles for different class I PI3K isoforms in controlling systemic metabolic homeostasis and energy balance are discussed. We conclude that defining the functional specificities and redundancies of different class I PI3K isoforms in pathways driving disease and controlling metabolic homeostasis is fundamental to develop novel PI3K-targeted therapies.

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  1. The Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345, Göteborg, Sweden

    Giovanni Solinas & Barbara Becattini

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    Margarita Dominguez-Villar

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Solinas, G., Becattini, B. (2022). PI3K and AKT at the Interface of Signaling and Metabolism. In: Dominguez-Villar, M. (eds) PI3K and AKT Isoforms in Immunity . Current Topics in Microbiology and Immunology, vol 436. Springer, Cham. https://doi.org/10.1007/978-3-031-06566-8_13

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