Cholera toxin inhibits T cell receptor signaling by covalent modification of the CD3-zeta subunit.
In the Jurkat T cell line, triggering of the TCR leads to activation of phospholipase C, resulting in an increase in inositol trisphosphate (IP3) release followed by a rise in intracellular Ca2+. This signaling pathway is interrupted by cholera toxin (CTX) treatment. To possibly explain this inhibition, we demonstrate that CTX can affect the TCR/CD3 complex itself by causing a covalent modification of the CD3-zeta subunit. After exposure of Jurkat cells to CTX, CD3-zeta increases its apparent m.w. and becomes more acidic in isoelectric focusing. The time course of the modification correlates well with the reduction in IP3 generation and Ca2+ release after CTX treatment, suggesting that the modification of zeta might be the cause of the impaired TCR/CD3 signaling. As is true for the CTX-mediated decrease in TCR signaling, the change in CD3-zeta was cAMP-independent and cannot be evoked by the enzymatically inactive CTX-B subunit alone.
Institute of Molecular Pharmacology, Hannover Medical School, Germany.
B M
BM
Haack
F
F
Emmrich
K
K
Resch
D017252:CD3 Complex / Q000032:analysis / Q000187:drug effects*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D002772:Cholera Toxin; D000242:Cyclic AMP