环磷酸腺苷通过依赖Raf-1和不依赖Raf-1的机制来阻止细胞生长。
Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms.
作者信息
Dumaz Nicolas, Light Yvonne, Marais Richard
机构信息
Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, London SW3 6JB, United Kingdom.
出版信息
Mol Cell Biol. 2002 Jun;22(11):3717-28. doi: 10.1128/MCB.22.11.3717-3728.2002.
Abstract
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.
摘要
普遍认为，环磷酸腺苷（cAMP）可通过使丝氨酸43位点的Raf-1磷酸化并抑制向细胞外信号调节蛋白激酶的信号传导来阻断细胞生长。我们发现，cAMP对Raf-1的抑制作用比先前报道的要复杂得多。当细胞内cAMP升高时，Raf-1在三个位点（S43、S233和S259）发生磷酸化，这些位点独立发挥作用来阻断Raf-1。Ras依赖性和Ras非依赖性过程均被破坏。然而，当在NIH 3T3细胞中表达对cAMP不敏感的Raf-1版本时，cAMP升高时其生长仍会受到强烈抑制。因此，尽管Raf-1似乎是cAMP的一个重要靶点，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。
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2
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Oncogene. 2001 Jul 5;20(30):3949-58. doi: 10.1038/sj.onc.1204526.
3
Rap1 signalling: adhering to new models.Rap1信号传导：遵循新模型。
Nat Rev Mol Cell Biol. 2001 May;2(5):369-77. doi: 10.1038/35073073.
4
Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene.缺乏c-raf-1基因的小鼠胚胎致死性和胎肝凋亡
EMBO J. 2001 Apr 17;20(8):1952-62. doi: 10.1093/emboj/20.8.1952.
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MEK kinase activity is not necessary for Raf-1 function.MEK激酶活性对于Raf-1功能并非必需。
EMBO J. 2001 Apr 17;20(8):1940-51. doi: 10.1093/emboj/20.8.1940.
6
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7
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8
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9
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10
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