Critical roles of the PI3K/Akt signaling pathway in T cell development

Marisa M. Juntilla, Gary A. Koretzky

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations

Abstract

Thymocyte development requires an integration of extracellular cues to enforce lineage commitment at multiple defined checkpoints in a stage-specific manner. Critical signals from the pre-TCR, Notch, and the receptor for interleukin-7 (IL-7) dictate cellular differentiation from the CD4-CD8- (double negative) stage to the CD4+CD8+ (double positive) stage. The PI3K/Akt signaling pathway is required to translate these extracellular signaling events into multiple functional outcomes including cellular survival, proliferation, differentiation, and allelic exclusion at the β-selection checkpoint. However, a complete understanding of the contributions made by the PI3K/Akt pathway in thymocyte development has not been straightforward. This review highlights studies that support the model that the PI3K/Akt pathway is essential for thymocyte survival. We provide new evidence that Akt-mediated survival is not solely due to the increased expression of Bcl-xL but also is a consequence of the role played by Akt to support metabolism in proliferating thymocytes.

Original languageEnglish (US)
Pages (from-to)104-110
Number of pages7
JournalImmunology Letters
Volume116
Issue number2
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Keywords

  • Akt
  • Bcl-xL
  • Metabolism
  • PI3K
  • TCR
  • Thymocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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