Signaling through CD43 regulates CD4 T-cell trafficking

Blood. 2007 Oct 15;110(8):2974-82. doi: 10.1182/blood-2007-01-065276. Epub 2007 Jul 16.

Abstract

The mucin-like protein CD43 is excluded from the immune synapse, and regulates T-cell proliferation as well as T-cell migration. While the CD43 cytoplasmic domain is necessary for regulation of T-cell activation and proliferation, the mechanism via which CD43 regulates trafficking is not well defined. To investigate whether CD43 phosphorylation regulates its function in T cells, we used tandem mass spectrometry and identified Ser76 in murine CD43 as a previously unidentified site of basal phosphorylation. Interestingly, mutation of this single serine to alanine greatly diminishes T-cell trafficking to the lymph node, while CD43 exclusion and CD43-mediated regulation of T-cell proliferation remain intact. Furthermore, the CD43 extracellular domain was also required for T-cell trafficking, providing a hitherto unknown function for the extracellular domain, and suggesting that the extracellular domain may be required to transduce signals via the cytoplasmic domain. These data reveal a novel mechanism by which CD43 regulates T-cell function, and suggest that CD43 functions as a signaling molecule, sensing extracellular cues and transducing intracellular signals that modulate T-cell function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Movement / immunology*
  • Conserved Sequence
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Leukosialin / chemistry
  • Leukosialin / genetics
  • Leukosialin / metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Tandem Mass Spectrometry
  • Transduction, Genetic

Substances

  • Leukosialin