Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection

Nat Immunol. 2004 Mar;5(3):289-98. doi: 10.1038/ni1038. Epub 2004 Feb 8.


Thymocyte selection and differentiation requires extracellular signal-regulated kinase (Erk) signaling, but transcription factor substrates of Erk in thymocytes are unknown. We have characterized the function of SAP-1 (Elk4), an Erk-regulated transcription factor, in thymocyte development. Early thymocyte development was normal, but single-positive thymocyte and peripheral T cell numbers were reduced, reflecting a T cell-autonomous defect. T cell receptor-induced activation of SAP-1 target genes such as Egr1 was substantially impaired in double-positive thymocytes, although Erk activation was normal. Analysis of T cell receptor transgenes showed that positive selection was reduced by 80-90% in SAP-1-deficient mice; heterozygous mice showed a moderate defect. Negative selection was unimpaired. SAP-1 thus directly links Erk signaling to the transcriptional events required for thymocyte positive selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / cytology
  • Thymus Gland / growth & development
  • Thymus Gland / immunology*
  • Transcription, Genetic
  • ets-Domain Protein Elk-4


  • DNA-Binding Proteins
  • Elk4 protein, mouse
  • Receptors, Antigen, T-Cell
  • ets-Domain Protein Elk-4
  • Mitogen-Activated Protein Kinases