Identification of a nuclear localization signal in suppressor of cytokine signaling 1
Identification of a nuclear localization signal in suppressor of cytokine signaling 1
复制标题
DOI：
10.1096/fj.08-116079
复制
发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Dalpke, Alexander H.
中科院分区：
文献类型：
--
作者：
Baetz, Andrea;Koelsche, Christian;Dalpke, Alexander H.
细胞因子信号抑制蛋白（Suppressor of cytokine signaling， SOCS）是janus激酶的诱导反馈抑制剂，也是转录信号通路的信号转导和激活因子。此外，SOCS1已被确定调节核nf - κ B亚基的稳定性。然而，关于SOCS1核池的监管细节尚不清楚。通过不同的实验方法，我们观察到SOCS1家族成员在不同细胞系中表达时定位于细胞核，而不是其他SOCS家族成员。在ifn - γ刺激的巨噬细胞中证实了内源性SOCS1的核转运。序列分析发现，在SOCS1的src-homology 2 （SH2）结构域和SOCS盒之间存在一个二部核定位信号（NLS）。删除该区域，引入一系列R/ a点突变，或将该序列替换为SOCS3的相应区域，导致核定位丢失。SOCS1-NLS与细胞因子诱导的含SH2区域蛋白（CIS）的融合导致该细胞质蛋白的核定位。丢失核定位的SOCS1突变体仍然有效抑制ifn - α介导的STAT1酪氨酸磷酸化。然而，它们对ifn - α介导的CD54诱导的抑制减弱。结果确定了迄今为止未知的SOCS1转运到细胞核，扩展了SOCS1抑制活性的频谱。-Baetz， A, Koelsche， C, Strebovsky， J, Heeg， K, Dalpke， A. H.细胞因子信号抑制因子核定位信号的鉴定[J]。中华医学杂志，22,4296-4305 （2008）
Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of janus kinase and signal transducer and activators of transcription signaling pathways. In addition, SOCS1 has been identified to regulate stability of nuclear NF-kappa B subunits. However, details about the regulation of the nuclear pool of SOCS1 are unknown. Using different experimental approaches, we observed that SOCS1 but no further SOCS family members localized to the nucleus when expressed in various cell lines. Nuclear transport was confirmed for endogenous SOCS1 in macrophages stimulated with IFN-gamma. Sequence analysis revealed a bipartite nuclear localization signal (NLS) located between the src-homology 2 (SH2) domain and the SOCS box of SOCS1. Deletion of this region, introduction of a series of R/A point mutations, or substitution of this sequence with the respective region of SOCS3 resulted in loss of nuclear localization. Fusion of the SOCS1-NLS to cytokine-inducible SH2 region containing protein (CIS) resulted in nuclear localization of this otherwise cytoplasmic protein. SOCS1 mutants with loss of nuclear localization were still effective in suppressing IFN-alpha-mediated STAT1 tyrosine phosphorylation. However, they showed decreased inhibition of IFN-alpha-mediated induction of CD54. The results identify a hitherto unknown transport of SOCS1 into the nucleus which extends the spectrum of SOCS1 inhibitory activity.-Baetz, A., Koelsche, C., Strebovsky, J., Heeg, K., Dalpke, A. H. Identification of a nuclear localization signal in suppressor of cytokine signaling 1. FASEB J. 22, 4296-4305 (2008)