Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms
Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms
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DOI：
10.1128/mcb.22.11.3717-3728.2002
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发表时间：
2002-06-01
影响因子：
5.3
通讯作者：
Marais, R
中科院分区：
文献类型：
--
作者：
Dumaz, N;Light, Y;Marais, R
环腺苷酸（cAMP）通过磷酸化Raf-1的丝氨酸43位，抑制细胞外信号调节蛋白激酶（ERK）信号传导，从而抑制细胞生长。我们表明，抑制Raf-1 cAMP是相当复杂的比以前报道的。当细胞cAMP升高时，Raf-1在三个残基（S43、S233和S259）上磷酸化，这三个残基独立地起作用以阻断Raf-1。Ras依赖和Ras独立的过程都被破坏。然而，当cAMP不敏感版本的Raf-1在NIH 3 T3细胞中表达时，当cAMP升高时，它们的生长仍然受到强烈抑制。因此，尽管Raf-1似乎是一个重要的cAMP靶点，但cAMP也靶向其他途径，提供了导致细胞生长抑制的替代机制。
It is widely accepted that cyclic AMP (cAMP) can block cell growth by phosphorylating Raf-1 on serine 43 and inhibiting signaling to extracellular signal-regulated protein kinase. We show that the suppression of Raf-1 by cAMP is considerably more complex than previously reported. When cellular cAMP is elevated, Raf-1 is phosphorylated on three residues (S43, S233, and S259), which work independently to block Raf-1. Both Ras-dependent and Ras-independent processes are disrupted. However, when cAMP-insensitive versions of Raf-1 are expressed in NIH 3T3 cells, their growth is still strongly suppressed when cAMP is elevated. Thus, although Raf-1 appears to be an important cAMP target, other pathways are also targeted by cAMP, providing alternative mechanisms that lead to suppression of cell growth.