Diffusion control of protein phosphorylation in signal transduction pathways
Diffusion control of protein phosphorylation in signal transduction pathways
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DOI：
10.1042/0264-6021:3500901
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发表时间：
2000-09-15
影响因子：
4.1
通讯作者：
Hoek, JB
中科院分区：
文献类型：
--
作者：
Kholodenko, BN;Brown, GC;Hoek, JB
多种信号蛋白在不同的细胞位置被磷酸化和去磷酸化，这可能导致细胞内磷酸化蛋白的空间梯度。我们已经推导出关系，使我们能够估计蛋白激酶，磷酸酶和信号蛋白的扩散控制蛋白磷酸化通量和磷酸化-蛋白梯度的程度。分析了两种不同的细胞几何结构：(1)激酶位于一个平面膜上，磷酸酶位于另一个平行平面膜上；(2)激酶位于球形细胞的质膜上，磷酸酶均匀分布在细胞质中。我们证明了蛋白质扩散的控制贡献是潜在的显著的，考虑到蛋白质激酶，磷酸酶和扩散的测量率。如果膜之间的距离为1 μ m或更大，则扩散控制可以达到33%或更多，其余的控制（67%）由激酶和磷酸酶共享。在小于0.1 μ m的距离内，扩散不限制蛋白磷酸化。对于半径为10 μ m的球形细胞，蛋白质扩散系数为10(-8)cm(2) s(-1)，激酶和磷酸酶的速率常数约为。1 s(-1)，磷酸化通量的控制主要在于磷酸酶和蛋白质扩散，两者的贡献大致相等。磷脂蛋白在细胞膜和细胞中心的浓度之比（磷脂蛋白的动态区隔）是由蛋白磷酸酶的速率和扩散速率控制的。该激酶对磷蛋白梯度绝对值的控制有重要作用。
Multiple signalling proteins are phosphorylated and dephosphorylated at separate cellular locations, which potentially causes spatial gradients of phospho-proteins within the cell. We have derived relationships that enable us to estimate the extent to which a protein kinase, a phosphatase and the diffusion of signalling proteins control the protein phosphorylation flux and the phospho-protein gradient. Two different cellular geometries were analysed: (1) the kinase is located on one planar membrane and the phosphatase on a second parallel planar membrane, and (2) the kinase is located on the plasma membrane of a spherical cell and the phosphatase is distributed homogeneously in the cytoplasm. We demonstrate that the control contribution of protein diffusion is potentially significant, given the measured rates for protein kinases, phosphatases and diffusion. If the distance between the membranes is 1 mu m or greater, the control by diffusion can reach 33 % or more, with the rest of the control (67 %) shared by the kinase and the phosphatase. At distances of less than 0.1 mu m, diffusion does not limit protein phosphorylation. For a spherical cell of radius 10 mu m, a protein diffusion coefficient of 10(-8) cm(2 .) s(-1) and rate constants for the kinase and the phosphatase of approx. 1 s(-1), control over the phosphorylation flux resides mainly with the phosphatase and protein diffusion, with approximately equal contributions of each of these. The ratio of phospho-protein concentrations at the cell membrane and the cell centre (the dynamic compartmentation of the phospho-protein) is shown to be controlled by the rates of the protein phosphatase and of diffusion. The kinase can contribute significantly to the control of the absolute value of the phosphoprotein gradient.