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CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development.

The kinase-phosphatase pair Csk and CD45 reciprocally regulate phosphorylation of the inhibitory tyrosine of the Src family kinases Lck and Fyn. T cell receptor (TCR) signaling and thymic development require CD45 expression but proceed constitutively in the absence of Csk. Here, we show that relative titration of CD45 and Csk expression reveals distinct regulation of basal and inducible TCR signaling during thymic development. Low CD45 expression is sufficient to rescue inducible TCR signaling and positive selection, whereas high expression is required to reconstitute basal TCR signaling and beta selection. CD45 has a dual positive and negative regulatory role during inducible but not basal TCR signaling. By contrast, Csk titration regulates basal but not inducible signaling. High physiologic expression of CD45 is thus required for two reasons-to downmodulate inducible TCR signaling during positive selection and to counteract Csk during basal TCR signaling.

Pubmed ID: 20346773


  • Zikherman J
  • Jenne C
  • Watson S
  • Doan K
  • Raschke W
  • Goodnow CC
  • Weiss A



Publication Data

March 26, 2010

Associated Grants

  • Agency: NIAMS NIH HHS, Id: K08 AR059723
  • Agency: NIAID NIH HHS, Id: P01 AI035297
  • Agency: NIAID NIH HHS, Id: P01 AI035297-180007
  • Agency: NIAID NIH HHS, Id: P01 AI35297
  • Agency: NIAID NIH HHS, Id: R01 AI052127
  • Agency: NIAID NIH HHS, Id: R01 AI052127-05
  • Agency: NIAID NIH HHS, Id: R01 AI074847
  • Agency: NIAID NIH HHS, Id: R01 AI074847-03
  • Agency: NIAID NIH HHS, Id: R01 AI52127
  • Agency: NIAID NIH HHS, Id: R01 AI74847
  • Agency: NIAID NIH HHS, Id: U19 AI100627
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alleles
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Antigens, CD45
  • Base Sequence
  • Cells, Cultured
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphotyrosine
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • Thymus Gland
  • src-Family Kinases