CAML is a p56Lck-interacting protein that is required for thymocyte development
CAML is a p56Lck-interacting protein that is required for thymocyte development
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DOI：
10.1016/j.immuni.2005.06.006
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发表时间：
2005-08-01
期刊：
影响因子：
32.4
通讯作者：
Bram, RJ
中科院分区：
文献类型：
--
作者：
Tram, DD;Edgar, CE;Bram, RJ
钙调节亲环蛋白配体 (CAML) 是一种广泛表达的蛋白质，与 T 细胞信号传导有关，但其在免疫系统中的机制和生理作用尚不清楚。我们在此表明 CAML 对于外周 T 细胞的发育至关重要。小鼠胸腺细胞中 CAML 的失活降低了双阳性和单阳性胸腺细胞的数量，同时伴随着阳性选择的减少和阴性选择的增强。我们发现 CAML 与 p56Lck 相互作用，并且似乎在静息细胞和 T 细胞受体 (TCR) 刺激的细胞中调节激酶的亚细胞定位。 CAML 缺陷细胞在 TCR 刺激后表现出增强的 p561ck 和 ZAP-70 磷酸化以及增加的 IL2 产生和细胞死亡，表明 CAML 可能充当 p561ck 的负调节因子。我们的数据确立了 CAML 作为胸腺生成过程中 T 细胞存活的重要介质的新作用，并表明它的缺失会解除 p56Lck 信号传导的调节。
Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein implicated in T cell signaling, although its mechanism and physiologic role in the immune system are unknown. We show here that CAML is essential for peripheral T cell development. Inactivation of CAML in mouse thymocytes lowered the numbers of double-positive and single-positive thymocytes, concomitant with reduced positive and enhanced negative selection. We found that CAML interacts with p56Lck and appears to regulate subcellular localization of the kinase in both resting and T cell receptor (TCR)-stimulated cells. CAML-deficient cells displayed enhanced p561ck and ZAP-70 phosphorylation and increased IL2 production and cell death after TCR stimulation, suggesting that CAML may act as a negative regulator of p561ck. Our data establish a novel role for CAML as an essential mediator of T cell survival during thymopoiesis and indicate that its loss deregulates p56Lck signaling.