Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades.
Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades.
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DOI：
10.1038/msb4100108
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发表时间：
2006
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
包括丝裂原活化蛋白激酶（MAPK）途径在内的蛋白激酶/磷酸酶级联反应的一个标志是其组分在细胞内的空间分离。顶层激酶MAP3K在细胞膜上被磷酸化，随后下游水平的细胞质激酶（MAP2K和MAPK）将信号传播到远处的靶标。考虑到测量到的蛋白质扩散率和磷酸酶活性，通过扩散传播的信号会导致MAP2K活性急剧下降，核附近的双磷酸化MAPK （ppMAPK）水平降低，特别是在大细胞中，如卵母细胞。在这里，我们证明了两个位点MAPK（去）磷酸化循环中的双稳定性产生了一种新型的磷蛋白波，这种波从表面传播到细胞内部。ppMAPK向细胞质MAP2K的正反馈增强了ppMAPK波的传播跨度，使磷酸化信号能够在极远的距离上传递。以恒定振幅和高速行进的磷酸化波的发现可能会解决发育神经元中长期存在的生存信号之谜。
A hallmark of protein kinase/phosphatase cascades, including mitogen-activated protein kinase (MAPK) pathways, is the spatial separation of their components within cells. The top-level kinase, MAP3K, is phosphorylated at the cell membrane, and cytoplasmic kinases at sequential downstream levels (MAP2K and MAPK) spread the signal to distant targets. Given measured protein diffusivity and phosphatase activities, signal propagation by diffusion would result in a steep decline of MAP2K activity and low bisphosphorylated MAPK (ppMAPK) levels near the nucleus, especially in large cells, such as oocytes. Here, we show that bistability in a two-site MAPK (de)phosphorylation cycle generates a novel type of phosphoprotein wave that propagates from the surface deep into the cell interior. Positive feedback from ppMAPK to cytoplasmic MAP2K enhances the propagation span of the ppMAPK wave, making it possible to convey phosphorylation signals over exceedingly long distances. The finding of phosphorylation waves traveling with constant amplitude and high velocity may solve a long-standing enigma of survival signaling in developing neurons.
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DOI：
10.1002/neu.10323
发表时间：
2004-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Howe, CL;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
64.8
作者：
Xiong, W;Ferrell, JE
通讯作者：
Ferrell, JE
影响因子：
16.2
作者：
Perlson, E;Hanz, S;Fainzilber, M
通讯作者：
Fainzilber, M
影响因子：
3.4
作者：
Khan, S;Jain, S;Trentham, DR
通讯作者：
Trentham, DR
影响因子：
3.2
作者：
Lipkow, K;Andrews, SS;Bray, D
通讯作者：
Bray, D