Phosphatidylinositol 3-kinase signaling in thymocytes: the need for stringent control

Sci Signal. 2010 Aug 17;3(135):re5. doi: 10.1126/scisignal.3135re5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Proliferation
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Models, Immunological*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction / physiology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology*

Substances

  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Phosphatidylinositol 3-Kinase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt