Comparative analysis of T-cell costimulation and CD43 activation reveals novel signaling pathways and target genes

Blood. 2004 Nov 15;104(10):3302-4. doi: 10.1182/blood-2004-04-1536. Epub 2004 Jul 27.

Abstract

The CD43 lymphocyte surface receptor is involved in the regulation of lymphocyte adhesion and activation. Many CD43 functions remain controversial or unclear, and it is not known to which extent CD43 signaling pathways are shared with or distinct from those used by the T-cell receptor (TCR). Here, we systematically compared signaling events and target gene expression induced by CD43 or T-cell costimulation in primary human peripheral T cells. These studies identify nuclear factor-kappaB (NF-kappaB) p65 serine 468 as a novel inducible phosphorylation site strongly induced by T-cell costimulation and only weakly triggered by CD43 ligation. We also identified CD43 as a novel Jun N-terminal kinase (JNK) activator and a comprehensive analysis of further signaling events suggests that both stimuli use overlapping but also distinct signaling pathways. Microarray analysis of inflammatory genes shows 1 group of genes coregulated by both stimuli and 2 further groups of target genes affected solely by costimulation or primarily by CD43.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • CD28 Antigens / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Leukosialin
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Sialoglycoproteins / metabolism*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transcription Factor RelA

Substances

  • Antigens, CD
  • CD28 Antigens
  • Leukosialin
  • NF-kappa B
  • Sialoglycoproteins
  • Transcription Factor RelA
  • UN1 sialoglycoprotein, human
  • JNK Mitogen-Activated Protein Kinases