Cell regulation: a time to signal, a time to respond.
Cell regulation: a time to signal, a time to respond.
复制标题
细胞调节：发出信号的时间，反应的时间。
DOI：
10.1002/bies.201200077
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Haugh,JasonM
中科院分区：
文献类型：
--
作者：
Haugh,JasonM
The behaviours of living cells are normally controlled by growth factors, cytokines, and other molecular cues in vivo, affecting cell division, migration, differentiation, and survival. Specific receptors on the cell surface recognize these cues and mobilize signal transduction networks, which constitute the intracellular machinery responsible for actuating and regulating functional responses. In cancer, certain proteins (oncogenes) are mutated so as to render the cell autonomous from external cues. Consequently, intracellular signalling is robust and uncontrolled, and thus so are cell proliferation, survival, and movement. It is therefore of paramount importance to understand the intricate mechanisms by which signal transduction networks are governed, but the problem is the daunting complexity at the molecular level. Even when considering a single pathway, one must wade through a morass of protein components and post-translational modifications to figure out how it is regulated.The encouraging news is that considerable progress over the past twenty years or so has resulted in a mature understanding of many signalling pathways. At least conceptually, this simplifies the problem by allowing us to treat pathways as modules, each responsible for the activation of a critical node in the network. Such ‘master regulators’ would include mitogenactivated protein kinases (MAPKs) and other important protein kinases such as Akt. Hence, the notion is that we can reduce the complexity of the problem by splitting it into two parts: one, the convergence of receptor-mediated pathways resulting in activation of a handful of master regulators, and two, the influences of those regulators on cell behaviour. With this paradigm, we can tackle each of the two parts independently and develop quantitative frameworks in which measurements are compared with mathematical models 1. Thus, it is envisioned that we will be able to predict the effects of molecular interventions in both normal and transformed cells, a prospect that is not lost on forward-thinking drug companies 2.
