CD43 is the most abundant costimulatory molecule on the T cell surface; it transduces activation signals through its cytoplasmic domain, modulating the outcome of T cell responses. CD43 KO mice revealed a positive role for CD43 in T cell migration and in the regulation of cell number and homeostasis. The aim of this study was to identify new signaling pathways modulated by CD43. Protein expression profiles of normal human CD4+ T cells stimulated through TCR and CD43 identified changes in 189 proteins. Bioinformatic analysis revealed that glucose metabolism was significantly represented. We evaluated pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, as well as glucose uptake. TCR+CD43 stimulated cells showed a 1.5 fold increase in PK activity, but only a moderate increase in LDH activity and glucose uptake. Interestingly, tyrosine phosphorylation of PK triggers its ability to phosphorylate Stat3. Phosphorylation of Y105 of PK and of Y705 of Stat3 was induced in response to TCR+CD43 and TCR+CD28. Since phosphorylation of Y705 of Stat3 by PK induces MEK5 transcription, we evaluated the MEK5/ERK5 pathway activation by measuring the levels of pCREB at S133, an ERK5 target. CREB pS133 was increased in TCR+CD43 and TCR+CD28 stimulated T cells. Altogether, our results show that CD43 regulates monosaccharide metabolism, as well as moonlight functions of metabolic enzymes.
- Copyright © 2013 by The American Association of Immunologists, Inc.