Venkataraman L, Burakoff S J, Sen R
Rosenstiel Research Center, Brandeis University, Waltham, Massachusetts 02254-9110.
J Exp Med. 1995 Mar 1;181(3):1091-9. doi: 10.1084/jem.181.3.1091.
Stimulation of B and T cells via the antigen receptor, by phorbol ester or by phorbol ester and ionomycin, leads to nuclear translocation of the inducible transcription factor NF-kappa B, comprising the p50 and p65 rel-related polypeptides. In this report we show that c-rel is a component of the antigen receptor-induced kappa B binding proteins in both B and T cells. Whereas NF-kappa B can be induced by phorbol ester alone, optimal induction of c-rel requires stimulation by both phorbol ester and ionomycin, the dual signal that is necessary for proliferation of untransformed lymphocytes. Furthermore, c-rel induction is blocked by the immunosuppressive drug FK506 that is known to inhibit B and T cell activation. c-rel-dependent transactivation of the interleukin-2 receptor alpha chain (IL-2R alpha) promoter is augmented by coexpression of calcineurin, suggesting the involvement of a calcineurin-dependent intracellular pathway. Our results identify c-rel as a target of immunosuppressive agents and illustrate the similarity of activation pathways in both B and T cells.
通过抗原受体、佛波酯或佛波酯与离子霉素刺激B细胞和T细胞，会导致诱导型转录因子NF-κB发生核转位，NF-κB由p50和p65 rel相关多肽组成。在本报告中，我们表明c-rel是B细胞和T细胞中抗原受体诱导的κB结合蛋白的一个组成部分。虽然单独的佛波酯就能诱导NF-κB，但c-rel的最佳诱导需要佛波酯和离子霉素共同刺激，这是未转化淋巴细胞增殖所必需的双重信号。此外，免疫抑制药物FK506可阻断c-rel的诱导，已知FK506能抑制B细胞和T细胞的激活。钙调神经磷酸酶的共表达增强了c-rel依赖的白细胞介素-2受体α链（IL-2Rα）启动子的反式激活，提示存在一条钙调神经磷酸酶依赖的细胞内途径。我们的结果确定c-rel是免疫抑制剂的作用靶点，并阐明了B细胞和T细胞激活途径的相似性。
