Phosphorylation Modulated Networks of the Cell

At any time, in any cell, multiple types of molecular networks are concurrently active. These networks are neither static nor are they independent. Thousands of proteins are simultaneously busy in our cells; some occur in great numbers, others in trifling quantities – which does not necessarily mean that they are less important. Perturbations of the cell induce coordinated changes in multiple networks and one of the predominant open questions in systems biology is how, exactly this coordination is achieved. In other words: how do cells process information. 

PhosphoNetX deals with the phosphorylation of proteins. Many of the multitude of signals received by the cell at any given time lead to the activation or deactivation of specific protein kinases/phosphatases. These in turn propagate the signal of specific cellular proteins and affect properties such as activity, interactions and cellular distribution. One known example is the tumor suppressor protein, p53. If a cell starts to divide uncontrollably and develops cancer-like characteristics, a phosphorylation of p53 causes the cell in question to "commit suicide" and thus banning the cancer risk.

One of the aims of PhosphNetX is to map out the basic wiring diagram of phosphorylation mediated informational networks in cells. To achieve this goal, protein network analysis and high throughput phenotypic screens are used to connect the kinases/phosphatases to the sensors and signaling systems that provide their respective signal input. Also, systematic silencing of the kinases/phosphatases and quantitative phosphoproteomics are used to identify substrates of each kinase/phosphatase. Thus, these enzymes can be connected to specific effectors of cellular function. A next step is to develop robust, sensitive and quantitatively accurate assays with sufficient throughput to measure phosphorylation dependent information fluxes in different cells under a multitude of biological processes. The ultimate goal is to apply these data and resources to four applied biological projects: cell cycle control, membrane trafficking, the response of cells to mechanical stress, and perturbed networks in cancer. 

Updated September 2012