Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-κB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain
Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-κB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain
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DOI：
10.1074/jbc.275.3.1902
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发表时间：
2000-01-21
影响因子：
4.8
通讯作者：
Altman, A
中科院分区：
文献类型：
--
作者：
Witte, S;Villalba, M;Altman, A
蛋白激酶C-θ（PKC θ）是一种钙离子非依赖性PKC亚型，在T淋巴细胞（和肌肉）中选择性表达，被认为在T细胞受体诱导的活化中起重要作用。为了更好地了解PRC θ的功能和调控，我们利用酵母双杂交系统鉴定了PKC θ相互作用蛋白。我们报告了一个编码一种新的335个氨基酸（37.5-kDa）的PKC θ相互作用蛋白PICOT的cDNA的分离和鉴定（对于（P）在bar KC-（i）在bar相互作用（c）在bar ousin（o）在bar f（t）在bar hioredoxin下）。PICOT在各种组织中表达，包括在T细胞中，在那里它与PKC θ共定位。PICOT的N-末端有一个硫氧还蛋白的同源结构域，这是与PKC相互作用所必需的。PICOT的C-末端区域与表达的序列标签数据库的比较揭示了一个新的结构域的两个串联重复序列，该结构域在植物和哺乳动物中高度保守。T细胞中全长PICOT（但不是其N-或C-末端片段）的瞬时过表达抑制c-Jun N-末端激酶（但不是细胞外信号调节激酶）和转录因子AP-1或NF-κ B的活化。这些研究结果表明，PICOT及其进化保守的同源物可能与多种生物体中的PKC相关激酶相互作用，其次，它在调节硫氧还蛋白系统的功能中发挥作用。
Protein kinase C-theta (PKC theta) is a Ca2+-independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PRC theta, we have employed the yeast two-hybrid system to identify PKC theta-interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37.5-kDa) PKC theta-interacting protein termed PICOT (for (P) under bar KC-(i) under bar nteracting (c) under bar ousin (o) under bar f (t) under bar hioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKC theta. PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC, Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N- or C-terminal fragments) in T cells inhibited the activation of c-Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-kappa B. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.