Comparative analysis of T-cell costimulation and CD43 activation reveals novel signaling pathways and target genes.
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.
Department of Chemistry and Biochemistry, University of Bern, Freiestr. 3, 3012 Bern, Switzerland.
Ivan
I
Mattioli
Oliver
O
Dittrich-Breiholz
Mark
M
Livingstone
Michael
M
Kracht
M Lienhard
ML
Schmitz
D015703:Antigens, CD / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051917:Leukosialin; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012795:Sialoglycoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051996:Transcription Factor RelA
D015703:Antigens, CD; D018106:CD28 Antigens; D051917:Leukosialin; D016328:NF-kappa B; C465014:SPN protein, human; D012795:Sialoglycoproteins; D051996:Transcription Factor RelA; D048031:JNK Mitogen-Activated Protein Kinases