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Critical Roles of the AKT Substrate Girdin in Disease Initiation and Progression

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Protein Modifications in Pathogenic Dysregulation of Signaling

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Abstract

Many studies conducted over the past several decades have firmly established the roles of the serine/threonine kinase AKT and its upstream regulator phosphatidylinositol 3-kinase (PI3K) in the progression of a wide variety of human diseases, including cancers and metabolic, psychiatric, neurodegenerative, and cardiovascular diseases. Sited downstream from various growth factors and their cognate receptors, dysregulation of the PI3K/AKT pathway (and its downstream substrates) is unambiguously linked to the etiology of the diseases, most of which frequently result from mutations in genes encoding the constituents of the pathway or their deregulated expression caused by aberrant promoter activation. These observations provided the rationale for the development of new drugs targeting AKT kinase. However, this approach became far more difficult than initially anticipated. Consequently, an alternative strategy has evolved to target AKT substrates that differentially and selectively regulate many cellular processes and are involved in the modulation and progression of diseases. In this chapter, we describe how alterations in the function of AKT substrates, which are generally not involved in directly driving disease, contribute to the modulation of those diseases. We principally focus on Girdin, an AKT substrate that is involved in the progression of cancer and neural disorders.

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Acknowledgments

The authors are supported by Grant-in-Aid for Scientific Research on Innovative Areas (22117005) (M.T.) and Grant-in-Aid for Young Scientists (20432255) (A.E.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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  1. Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Atsushi Enomoto, Liang Weng & Masahide Takahashi

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  1. Atsushi Enomoto
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  2. Liang Weng
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  3. Masahide Takahashi
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Correspondence to Masahide Takahashi .

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  1. Division of Cellular & Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Jun-ichiro Inoue

  2. The Institute of Medical Science Division of Cell Signaling & Molecular Medicine, The University of Tokyo, Tokyo, Japan

    Mutsuhiro Takekawa

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Enomoto, A., Weng, L., Takahashi, M. (2015). Critical Roles of the AKT Substrate Girdin in Disease Initiation and Progression. In: Inoue, Ji., Takekawa, M. (eds) Protein Modifications in Pathogenic Dysregulation of Signaling. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55561-2_15

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