Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression.
Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression.
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DOI：
10.1126/scisignal.2003743
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发表时间：
2013-07-16
影响因子：
7.3
通讯作者：
DiCorleto PE
中科院分区：
文献类型：
--
作者：
Chandrasekharan UM;Dechert L;Davidson UI;Waitkus M;Mavrakis L;Lyons K;Beach JR;Li X;Egelhoff TT;Fox PL;DiCorleto PE
肿瘤坏死因子α（TNF-α）通过激活TNF受体1（TNFR 1，也称为p55）和TNFR 2（也称为p75）发挥其生物学活性。两种受体的活性都是TNF-α诱导的促炎反应所必需的。衔接蛋白TNFR相关因子2（TRAF 2）对于p55或p75介导的核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号传导的活化以及靶基因表达至关重要。在这里，我们确定了非肌肉肌球蛋白II（肌球蛋白）作为p75的结合伴侣。在肌球蛋白调节轻链（MRLC，肌球蛋白的一种组分）缺陷的细胞中，p75的TNF-α依赖性信号传导和靶基因表达的诱导持续时间比肌球蛋白丰富的细胞长得多。在静息内皮细胞中，肌球蛋白与p75的细胞内区域组成性结合，该区域与TRAF 2结合结构域重叠，TNF-α导致肌球蛋白从p75快速解离。在暴露于TNF-α后的早期时间点，p75激活Rho相关激酶1（ROCK 1）。ROCK 1活性的抑制阻断了MRLC的TNF-α依赖性磷酸化和肌球蛋白与p75的解离。ROCK 1依赖性肌球蛋白释放是TNF-α依赖性TRAF 2向p75募集和p75特异性NF-κB和MAPK信号转导激活所必需的。因此，我们的研究结果揭示了肌球蛋白在细胞因子信号传导中的一种以前未被表征的、非经典的调节功能。
Tumor necrosis factor α (TNF-α) elicits its biological activities through activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as p75). The activities of both receptors are required for the TNF-α–induced proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is critical for either p55- or p75-mediated activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression. Here, we identified nonmuscle myosin II (myosin) as a binding partner of p75. TNF-α–dependent signaling by p75 and induction of target gene expression persisted for substantially longer in cells deficient in myosin regulatory light chain (MRLC, a component of myosin) than in cells replete in myosin. In resting endothelial cells, myosin was bound constitutively to the intracellular region of p75, a region that overlaps with the TRAF2-binding domain, and TNF-α caused the rapid dissociation of myosin from p75. At early time points after exposure to TNF-α, p75 activated Rho-associated kinase 1 (ROCK1). Inhibition of ROCK1 activity blocked TNF-α–dependent phosphorylation of MRLC and the dissociation of myosin from p75. ROCK1-dependent release of myosin was necessary for the TNF-α–dependent recruitment of TRAF2 to p75 and for p75-specific activation of NF-κB and MAPK signaling. Thus, our findings have revealed a previously uncharacterized, noncanonical regulatory function of myosin in cytokine signaling.
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影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
DOI：
10.1016/j.bbrc.2010.05.084
发表时间：
2010-07-16
影响因子：
3.1
作者：
Bajaj, Gaurav;Rodriguez-Proteau, Rosita;Ishmael, Jane E.
通讯作者：
Ishmael, Jane E.
影响因子：
10.5
作者：
Kant, Shashi;Swat, Wojciech;Davis, Roger J.
通讯作者：
Davis, Roger J.
DOI：
10.1084/jem.188.7.1343
发表时间：
1998-10-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Douni E;Kollias G
通讯作者：
Kollias G
DOI：
10.1073/pnas.90.6.2532
发表时间：
1993-03-15
影响因子：
11.1
作者：
BROWN, K;PARK, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U