Ubiquitin-like protein MNSFβ regulates TLR-2-mediated signal transduction
Ubiquitin-like protein MNSFβ regulates TLR-2-mediated signal transduction
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DOI：
10.1007/s11010-011-1202-x
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发表时间：
2012-05-01
影响因子：
4.3
通讯作者：
Watanabe, Natsuko
中科院分区：
文献类型：
--
作者：
Nakamura, Morihiko;Watanabe, Jun;Watanabe, Natsuko
单克隆非特异性抑制因子β（MNSF β）的翻译后修饰参与了多种细胞过程的调节。先前的研究表明，MNSF β共价结合细胞内促凋亡蛋白Bcl-G，并调节TLR-4介导的信号转导。最近，我们发现，MNSF β也共价结合到endophilin II，endophilin A家族的成员，并抑制IKK激活的信号通路上游，但不是TLR-2信号的下游。在这项研究中，我们进一步研究了MNSF β在巨噬细胞样细胞系Raw 264.7细胞中TLR-2介导的信号转导中的作用机制。尽管MNSF beta siRNA增强了Pam（3）CDK（4）（TLR-2特异性配体）刺激的TNF α产生，但Bcl-G siRNA没有影响。MNSF β cDNA抑制Pam（3）CDK（4）刺激的TNF α产生。在Pam（3）CDK（4）刺激的Raw 264.7细胞中诱导高分子量（130 kDa）MNSF β-加合物。这种MNSF β-加合物不被LPS诱导，表明TLR-2介导的信号转导的特异性。在BALB/c腹腔巨噬细胞中观察到类似的观察结果。有趣的是，40-kDa MNSF β-加合物被Pam（3）CDK（4）刺激酪氨酸磷酸化。总之，新型MNSF β-加合物可以调节巨噬细胞中TLR-2信号通路。
Post-translational modification by monoclonal nonspecific suppressor factor beta (MNSF beta) has been involved in the regulation of a variety of cellular processes. Previous studies have demonstrated that MNSF beta covalently binds to the intracellular pro-apoptotic protein Bcl-G and regulates TLR-4-mediated signal transduction. Recently, we found that MNSF beta also covalently conjugates to endophilin II, a member of the endophilin A family, and inhibits the signal pathway upstream of IKK activation, but not downstream of TLR-2 signaling. In this study, we further examined the mechanism of action of MNSF beta in TLR-2-mediated signal transduction in macrophage-like cell line Raw264.7 cells. Although MNSF beta siRNA enhanced Pam(3)CDK(4) (TLR-2-specific ligand)-stimulated TNF alpha production, Bcl-G siRNA did not affect. MNSF beta cDNA inhibited the Pam(3)CDK(4)-stimulated TNF alpha production. High-molecular weight (130 kDa) MNSF beta-adduct was induced in Pam(3)CDK(4)-stimulated Raw264.7 cells. This MNSF beta-adduct was not induced by LPS, indicative of the specificity of TLR-2-mediated signal transduction. Similar observations were seen in BALB/c peritoneal macrophages. Interestingly, 40-kDa MNSF beta-adduct was tyrosine phosphorylated by Pam(3)CDK(4) stimulation. Collectively, novel MNSF beta-adducts may regulate TLR-2 signaling pathway in macrophages.