DEFECTIVE CAMP-DEPENDENT PHOSPHORYLATION OF INTACT LYMPHOCYTES-T IN ACTIVE SYSTEMIC LUPUS-ERYTHEMATOSUS
DEFECTIVE CAMP-DEPENDENT PHOSPHORYLATION OF INTACT LYMPHOCYTES-T IN ACTIVE SYSTEMIC LUPUS-ERYTHEMATOSUS
复制标题
DOI：
10.1073/pnas.87.5.1978
复制
发表时间：
1990-03-01
影响因子：
11.1
通讯作者：
KAMMER, GM
中科院分区：
文献类型：
--
作者：
HASLER, P;SCHULTZ, LA;KAMMER, GM
本研究旨在确定活动期系统性红斑狼疮(SLE)患者T淋巴细胞内源性底物cAMP依赖的磷酸化是否受损。在正常人T淋巴细胞中，细胞通透性cAMP类似物N6，O2‘-二丁酰腺苷3’，5‘-环一磷酸在一维SDS/PAGE上诱导底物磷酸化，其分子质量分别为17.5，23/25，33.5 kDa。磷酸化高峰出现在60min。与健康T细胞相比，活跃的SLE T细胞(n=8)在17.5 kDa底物中60min的底物磷酸化程度仅为15%，在23/25 kDa底物中为21%，在33.5 kDa底物中为9%。风湿性疾病对照组(类风湿性关节炎；原发性干燥综合征；n=8)在健康T细胞中的磷酸化平均分别为72%、124%和85%。由于cAMP唯一已知的作用机制是通过cAMP依赖的蛋白激酶(蛋白激酶A)，这些数据增加了SLE T淋巴细胞中该激酶水平缺陷的可能性。
The present study was undertaken to establish whether cAMP-dependent phosphorylation of endogenous substrates is impaired in T lymphocytes from subjects with active systemic lupus erythematosus (SLE). In normal human T lymphocytes, the cell-permeable cAMP analog, N6,O2''-dibutyryladenosine 3'',5''-cyclic monophosphate, induced phosphorylation of substrates with molecular masses of 17.5, 23/25, 33.5 kDa on one-dimensional SDS/PAGE. Maximal phosphorylation occurred at 60 min. In contrast to healthy T cells, the extent of substrate phosphorylation achieved in active SLE T cells (n = 8) was only 15% at 60 min in the 17.5-kDa substrate, 21% in the 23/25-kDa substrate, and 9% in the 33.5-kDa substrate. The rheumatic disease controls (rheumatoid arthritis; primary Sjogren syndrome; n = 8) exhibited a mean 72%, 124%, and 85%, respectively, of phosphorylation observed in healthy T cells. Because the only known mechanism by which cAMP acts is via cAMP-dependent protein kinase (protein kinase A), these data raise the possibility of a defect at the level of this kinase in SLE T lymphocytes.