Phosphoinositide 3-kinase and the mammalian target of rapamycin pathways control T cell migration

Ann N Y Acad Sci. 2010 Jan;1183:149-57. doi: 10.1111/j.1749-6632.2009.05134.x.

Abstract

The established role for phosphatidylinositol (3,4,5) triphosphate (PI(3,4,5)P3) signaling pathways is to regulate cell metabolism. More recently it has emerged that PI(3,4,5)P3 signaling via mammalian target of rapamycin and Foxo transcription factors also controls lymphocyte trafficking by determining the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. In quiescent T cells, nonphosphorylated active Foxos maintain expression of KLF2, a transcription factor that regulates expression of the chemokine receptors CCR7 and sphingosine 1 phosphate receptor, and the adhesion receptor CD62L that together control T-cell transmigration into secondary lymphoid tissues. PI(3,4,5)P3 mediates activation of protein kinase B, which phosphorylates and inactivates Foxos, thereby terminating expression of KLF2 and its target genes. The correct localization of lymphocytes is essential for effective immune responses, and the ability of phosphoinositide 3-kinase and mammalian target of rapamycin to regulate expression of chemokine receptors and adhesion molecules puts these signaling molecules at the core of the molecular mechanisms that control lymphocyte trafficking.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemotaxis, Leukocyte* / genetics
  • Gene Expression Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology*
  • L-Selectin / genetics
  • L-Selectin / metabolism
  • L-Selectin / physiology
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*
  • TOR Serine-Threonine Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • L-Selectin
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt