Phosphorylation of FADD/MORT1 at serine 194 and association with a 70-kDa cell cycle-regulated protein kinase
Phosphorylation of FADD/MORT1 at serine 194 and association with a 70-kDa cell cycle-regulated protein kinase
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DOI：
10.4049/jimmunol.164.3.1236
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Peter, ME
中科院分区：
文献类型：
--
作者：
Scaffidi, C;Volkland, J;Peter, ME
Fas相关死亡结构域蛋白(FADD)/受体诱导毒性介体-1(MORT1)是凋亡诱导受体CD95(APO-1/Fas)信号转导的关键分子，它连接激活的受体和效应物caspase-8，FADD还在胚胎发育和T细胞的细胞周期重入中发挥作用。FADD在丝氨酸残基上被磷酸化。我们现在发现磷酸化只发生在丝氨酸194，FADD的磷酸化被发现与细胞周期相关。在用诺康唑阻滞于G(2)/M交界处的细胞中，FADD被定量地磷酸化，而在用羟基脲滞留于G(1)/S的细胞中，只有非磷酸化的FADD被发现。在这种情况下，我们发现了一个70 kDa的细胞周期调节激酶，它与FADD的C末端部分特异结合，因为CD95介导的细胞凋亡不依赖于细胞周期，FADD的磷酸化可能调节其不依赖于细胞凋亡的功能。
The adapter molecule Fas-associated death domain protein (FADD)/mediator of receptor-induced toxicity-1 (MORT1) is essential for signal transduction of the apoptosis-inducing receptor CD95 (APO-1/Fas) as it connects the activated receptor with the effector caspase-8, FADD also plays a role in embryonic development and the cell cycle reentry of T cells. FADD is phosphorylated at serine residues. We now show that phosphorylation exclusively occurs at serine 194, The phosphorylation of FADD was found to correlate with the cell cycle. In cells arrested at the G(2)/M boundary with nocodazole, FADD was quantitatively phosphorylated, whereas only nonphosphorylated FADD was found in cells arrested in G(1)/S with hydroxyurea, in this context, we have identified a 70-kDa cell cycle-regulated kinase that specifically binds to the C-terminal half of FADD, Because CD95-mediated apoptosis is independent of the cell cycle, phosphorylation of FADD may regulate its apoptosis-independent functions.