Oscillatory phosphorylation of yeast Fus3 MAP kinase controls periodic gene expression and morphogenesis.
Oscillatory phosphorylation of yeast Fus3 MAP kinase controls periodic gene expression and morphogenesis.
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DOI：
10.1016/j.cub.2008.09.027
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发表时间：
2008-11-11
期刊：
影响因子：
--
通讯作者：
Levchenko A
中科院分区：
文献类型：
--
作者：
Hilioti Z;Sabbagh W Jr;Paliwal S;Bergmann A;Goncalves MD;Bardwell L;Levchenko A
信号转导网络可以表现出复杂的动态行为，如关键组分活动的振荡，但通常不清楚这种动态复杂性是否对网络的调节功能真正重要。本研究发现，丝裂原活化蛋白激酶（MAPK） Fus3是酵母交配信息素反应的关键调节因子，在持续的信息素暴露过程中，其磷酸化/激活状态持续振荡。这些MAPK活性振荡导致相应的交配基因表达振荡。MAPK活性和基因表达的振荡需要g蛋白信号Sst2的负调控，部分需要MAPK磷酸酶Msg5。Fus3激活的峰值与细胞形态发生的周期性回合相关，每个峰值在形成额外的交配投射之前。防止突起的形成并不能消除MAPK振荡，但防止MAPK振荡阻断了额外突起的形成。建立了一个数学模型，再现了观测到的振荡动力学的几个特征。这些观察结果证明了MAPK活性振荡在驱动周期性下游反应中的作用，并解释了信息素信号通路如何在1-3小时后脱敏，从而控制持续更长时间的形态变化。
Signal transduction networks can display complex dynamic behavior such as oscillations in the activity of key components, but it is often unclear if such dynamic complexity is actually important for the network's regulatory functions. Here we found that the mitogen-activated protein kinase (MAPK) Fus3, a key regulator of the yeast mating pheromone response undergoes sustained oscillations in its phosphorylation/activation state during continuous pheromone exposure. These MAPK activity oscillations led to corresponding oscillations in mating gene expression. Oscillations in MAPK activity and gene expression required the negative regulator of G-protein signaling Sst2, and partially required the MAPK phosphatase Msg5. Peaks in Fus3 activation correlated with periodic rounds of cell morphogenesis, with each peak preceding the formation of an additional mating projection. Preventing projection formation did not eliminate MAPK oscillation, but preventing MAPK oscillation blocked the formation of additional projections. A mathematical model was developed that reproduced several features of the observed oscillatory dynamics. These observations demonstrate a role for MAPK activity oscillation in driving a periodic downstream response, and explain how the pheromone signaling pathway, previously thought to desensitize after 1-3 hours, controls morphology changes that continue for a much longer time.
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DOI：
10.1073/pnas.142034399
发表时间：
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影响因子：
11.1
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发表时间：
1993-09-15
影响因子：
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通讯作者：
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影响因子：
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