Identification and characterization of a general nuclear translocation signal in signaling proteins
Identification and characterization of a general nuclear translocation signal in signaling proteins
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DOI：
10.1016/j.molcel.2008.08.007
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发表时间：
2008-09-26
期刊：
影响因子：
16
通讯作者：
Seger, Rony
中科院分区：
文献类型：
--
作者：
Chuderland, Dana;Konson, Alexander;Seger, Rony
受到刺激后，许多蛋白质转运到细胞核中，以调节各种细胞过程。由于许多这些蛋白质缺乏典型的核定位信号（NILS），因此易位的机制尚不清楚。我们在细胞外信号调节激酶(ERK)-2中寻找另一种机制，并发现了一个3个氨基酸结构域（SPS），该结构域在刺激下被磷酸化，从而诱导ERK2的核易位。一个包含这个磷酸化结构域的19个氨基酸延伸区自主地将不扩散的蛋白质插入细胞核。磷酸化的SPS通过与importin7结合并从核孔蛋白中释放而起作用。这使得它在被动和主动ERK转运中都能发挥作用。类似的结构域出现在许多细胞核穿梭蛋白中，我们发现SMAD3或MEK1中类似序列的磷酸化也诱导了它们的核积累。因此，我们的研究结果表明，这种磷酸化结构域作为一般的核序列定位信号（NTS）。
Upon stimulation, many proteins translocate into the nucleus in order to regulate a variety of cellular processes. The mechanism underlying the translocation is not clear since many of these proteins lack a canonical nuclear localization signal (NILS). We searched for an alternative mechanism in extracellular signal-regulated kinase (ERK)-2 and identified a 3 amino acid domain (SPS) that is phosphorylated upon stimulation to induce nuclear translocation of ERK2. A 19 amino acid stretch containing this phosphorylated domain inserts nondiffusible proteins to the nucleus autonomously. The phosphorylated SPS acts by binding to importin7 and the release from nuclear pore proteins. This allows its functioning both in passive and active ERK transports. A similar domain appears in many cytonuclear shuttling proteins, and we found that phosphorylation of similar sequences in SMAD3 or MEK1 also induces their nuclear accumulation. Therefore, our findings show that this phosphorylated domain acts as a general nuclear trainslocation signal (NTS).