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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.

Original publication

DOI

10.1126/scisignal.3135re5

Type

Journal article

Journal

Sci Signal

Publication Date

17/08/2010

Volume

3

Keywords

Cell Proliferation, Hematopoietic Stem Cells, Models, Immunological, Phosphatidylinositol 3-Kinase, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction, T-Lymphocytes, Thymus Gland