Phosphatidylinositol 3-kinase signaling in thymocytes: the need for stringent control.
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.
Fayard
Elisabeth
E
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. elisabeth.fayard@fmi.ch
Moncayo
Gerald
G
Hemmings
Brian A
BA
Holländer
Georg A
GA
D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D018448:Models, Immunological; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D058539:Phosphatidylinositol 3-Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt