Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings
Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings
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DOI：
10.1016/j.bbrc.2005.05.074
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发表时间：
2005-07-22
影响因子：
3.1
通讯作者：
Sytkowski, AJ
中科院分区：
文献类型：
--
作者：
Chen, CM;Sytkowski, AJ
Raf-1在细胞增殖、分化和存活中起重要作用。然而，Raf-1的独特和基本功能是抗凋亡。介导Raf-1抗凋亡功能的分子尚不清楚。在筛选Raf-1新底物的过程中，我们发现Raf-1激酶结构域在酵母双杂交系统中与ALG-2相互作用。我们进一步的研究表明，Raf-1磷酸化ALG-2在体外激酶试验。我们还发现，凋亡信号调节激酶1（ASK1）强烈磷酸化ALG-2。重要的是，Raf-1阻断ASK1依赖性ALG-2磷酸化。由于ALG-2与ASK1相关，并且ASK1和ALG-2都参与凋亡，我们的观察表明Raf-1可能通过中断ASK1依赖的ALG-2磷酸化来介导其抗凋亡功能。(c)2005年爱思唯尔公司All rights reserved.
Raf-1 plays important roles in cell proliferation, differentiation, and survival. However, the unique and essential function of Raf-1 is anti-apoptotic. The molecules that mediate Raf-1's anti-apoptotic function are not known. In the course of identifying new substrates of Raf-1, we found that the Raf-1 kinase domain interacted with apoptosis-linked gene-2 (ALG-2) in yeast two-hybrid system. Our further studies showed that Raf-1 phosphorylated ALG-2 in an in vitro kinase assay. We also found that apoptosis signal-regulating kinase 1 (ASK1) strongly phosphorylated ALG-2. Importantly, Raf-1 blocks the ASK1-dependent ALG-2 phosphorylation. Since ALG-2 associates with ASK1, and both ASK1 and ALG-2 are involved in apoptosis, our observations indicate that Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2. (c) 2005 Elsevier Inc. All rights reserved.