Haack B M, Emmrich F, Resch K
Institute of Molecular Pharmacology, Hannover Medical School, Germany.
J Immunol. 1993 Apr 1;150(7):2599-606.
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.
在Jurkat T细胞系中，TCR的触发会导致磷脂酶C的激活，从而使三磷酸肌醇（IP3）释放增加，随后细胞内Ca2+浓度升高。该信号通路会被霍乱毒素（CTX）处理所阻断。为了可能解释这种抑制作用，我们证明CTX可通过对CD3-ζ亚基进行共价修饰来影响TCR/CD3复合物本身。将Jurkat细胞暴露于CTX后，CD3-ζ的表观分子量增加，并且在等电聚焦中变得更具酸性。这种修饰的时间进程与CTX处理后IP3生成和Ca2+释放的减少密切相关，表明ζ的修饰可能是TCR/CD3信号受损的原因。正如CTX介导的TCR信号减少一样，CD3-ζ的变化不依赖于cAMP，并且不能仅由无酶活性的CTX-B亚基引起。
