The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development

Nat Immunol. 2004 May;5(5):539-45. doi: 10.1038/ni1062. Epub 2004 Apr 11.

Abstract

T lymphocyte activation is associated with activation of diverse AGC serine kinases (named after family members protein kinase A, protein kinase G and protein kinase C). It has been difficult to assess the function of these molecules in T cell development with simple gene-deletion strategies because different isoforms of AGC kinases are coexpressed in the thymus and have overlapping, redundant functions. To circumvent these problems, we explored the consequences of genetic manipulation of phosphoinositide-dependent kinase 1 (PDK1), a rate-limiting 'upstream' activator of AGC kinases. Here we analyzed the effect of PDK1 deletion on T lineage development. We also assessed the consequences of reducing PDK1 levels to 10% of normal. Complete PDK1 loss blocked T cell differentiation in the thymus, whereas reduced PDK1 expression allowed T cell differentiation but blocked proliferative expansion. These studies show that AGC family kinases are essential for T cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Gene Deletion
  • Integrases / genetics
  • Integrases / metabolism
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology
  • Mice
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • T-Lymphocytes / physiology*
  • Thymus Gland / physiology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Viral Proteins
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Pdpk1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Cre recombinase
  • Integrases