Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA.
Biophys J. 2011 Dec 7;101(11):2572-81. doi: 10.1016/j.bpj.2011.10.025.
The extracellular signal-regulated kinase (ERK) controls cellular processes by phosphorylating multiple substrates. The ERK protein can use the same domains to interact with phosphatases, which dephosphorylate and deactivate ERK, and with substrates, which connect ERK to its downstream effects. As a consequence, substrates can compete with phosphatases and control the level of ERK phosphorylation. We propose that this effect can qualitatively change the dynamics of a network that controls ERK activation. On its own, this network can be bistable, but in a larger system, where ERK accelerates the degradation of a substrate competing with a phosphatase, this network can oscillate. Previous studies proposed that oscillatory ERK signaling requires a negative feedback in which active ERK reduces the rate at which it is phosphorylated by upstream kinase. We argue that oscillations can also emerge even when this rate is constant, due to substrate-dependent control of ERK phosphorylation.
细胞外信号调节激酶（ERK）通过磷酸化多种底物来控制细胞过程。ERK 蛋白可以使用相同的结构域与磷酸酶相互作用，磷酸酶使 ERK 去磷酸化并失活，与底物相互作用，将 ERK 与其下游效应连接起来。因此，底物可以与磷酸酶竞争，控制 ERK 磷酸化水平。我们提出，这种效应可以定性地改变控制 ERK 激活的网络的动态。单独来看，这个网络可以是双稳态的，但在一个更大的系统中，ERK 加速了与磷酸酶竞争的底物的降解，这个网络可以振荡。先前的研究提出，振荡的 ERK 信号需要负反馈，其中活性 ERK 降低其被上游激酶磷酸化的速率。我们认为，即使这个速率是恒定的，由于 ERK 磷酸化的底物依赖性控制，振荡也可以出现。
