Why cytoplasmic signalling proteins should be recruited to cell membranes
Why cytoplasmic signalling proteins should be recruited to cell membranes
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DOI：
10.1016/s0962-8924(00)01741-4
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发表时间：
2000-05-01
影响因子：
19
通讯作者：
Westerhoff, HV
中科院分区：
文献类型：
--
作者：
Kholodenko, BN;Hoek, JB;Westerhoff, HV
有人认为，信号转导蛋白靠近细胞膜的定位会导致它们在激活后相遇率的增加。我们认为，这种增加的第一次遇到率是太小，负责真正增强信号转导。相反，膜定位的功能是增加同源信号转导蛋白之间的复合物的数量（或平均寿命），从而增加下游过程的激活程度。这是通过将蛋白质浓缩在质膜正下方的小体积区域中来实现的。信号转导链被简单地视为在低默认强度下工作，因为它的一个组分以低浓度存在。通过增加该组分的浓度，该链的稳定信号传导水平增强1000倍。这发生在“背驮”结合到膜蛋白，如激活的受体，启动信号转导链。为了产生这种效应，转移到膜上的蛋白质不能是游离的，而是必须通过与受体、膜脂质或支架的背驮结合来保持组织化。我们讨论了一个重要的结构约束施加这种机制的信号转导蛋白，也可能占衔接蛋白的存在。
It has been suggested that localization of signal-transduction proteins close to the cell membrane causes an increase in their rate of encounter after activation. We maintain that such an increase in the first-encounter rate is too small to be responsible for truly enhanced signal transduction. Instead, the function of membrane localization is to increase the number (or average lifetime) of complexes between cognate signal transduction proteins and hence increase the extent of activation of downstream processes. This is achieved by concentrating the proteins in the small volume of the area just below the plasma membrane. The signal-transduction chain is viewed simply as operating at low default intensity because one of its components is present at a low concentration. The steady signalling level of the chain is enhanced 1000-fold by increasing the concentration of that component. This occurs upon 'piggyback' binding to a membrane protein, such as the activated receptor, initiating the signal-transduction chain. For the effect to occur, the protein translocated to the membrane cannot be free but has to remain organized by being piggyback bound to a receptor, membrane lipid(s) or scaffold. We discuss an important structural constraint imposed by this mechanism on signal transduction proteins that might also account for the presence of adaptor proteins.