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Sci. Signal., 17 August 2010
Vol. 3, Issue 135, p. re5
[DOI: 10.1126/scisignal.3135re5]

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Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control

Elisabeth Fayard1*, Gerald Moncayo1, Brian A. Hemmings1*, and Georg A. Holländer2

1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
2 Pediatric Immunology, Center for Biomedicine, Department of Clinical-Biological Sciences, The University of Basel and The University Children’s Hospital, Mattenstrasse 28, CH-4058 Basel, Switzerland.

Abstract: The thymus serves as the primary site for the lifelong formation of new T lymphocytes; hence, it is essential for the maintenance of an effective immune system. Although thymocyte development has been widely studied, the mechanisms involved are incompletely defined. A comprehensive understanding of the molecular events that control regular thymocyte development will not only shed light on the physiological control of T cell differentiation but also probably provide insight into the pathophysiology of T cell immunodeficiencies, the molecular basis that underpins autoimmunity, and the mechanisms that instigate the formation of T cell lymphomas. Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide–dependent protein kinase (PDK1)–protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically.

* Corresponding authors. E-mail: brian.hemmings{at}fmi.ch (B.A.H.); elisabeth.fayard{at}fmi.ch (E.F.)

Citation: E. Fayard, G. Moncayo, B. A. Hemmings, G. A. Holländer, Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control. Sci. Signal. 3, re5 (2010).

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