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Prof. dr. Sacco de Vries
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General Introduction
All organisms use complex sensing systems to measure widely different parameters such as light, temperature, food, hormones and many other compounds including many different signaling molecules. Signal transduction systems are very ancient components of cells, reflected in the high level of conservation seen between the protein sequences of receptors in bacteria and those employed by plants and in our own bodies.
Many receptors are located in the plasma membrane when they are designed to perceive an extracellular signal. Others function directly in the nucleus where they can respond to the presence of a signal immediately by turning on or off target genes. Many receptors employ the posttranscriptional modification of phosphorylation to switch between active and inactive mode.
An important aspect of signal transduction is that the proteins involved, including the receptors themselves, are part of protein complexes. Such complexes aid in the integration of different signals, preventing or promoting cross talk between signals, serving different response systems with the same signal and in adjusting sensitivity. Many classical examples of signal transduction systems are to be found in textbooks such as 'Biochemistry' by Berg. Notable is that diseases such as cancer or obesity can often be traced back to deregulation of signaling systems.
It is for these reasons that in Biochemistry the topic of Signal Transduction is at the core of the biological problems that we address. It may appear that such a topic represents a well-trodden path and that little new information can be obtained. That this is not the case is evidenced by for instance recent findings in animal and plant signaling systems which shows that continuous recycling of plasma membrane receptors between the membrane and internal membrane compartments is as important in transducing the signal as phosphorylation is. These findings reinforce the concept that one needs to study biochemical processes inside intact cells to confirm or disprove findings done with isolated proteins.
In animal signal transduction we currently have one project that is aimed at human and mouse nuclear receptors that perceive fatty acids. This group of receptors, referred to as PPAR and RXR receptors are found in liver cells. We are visualizing these receptor proteins by fusing the encoding DNA sequences with GFP variants with the aim of following the assembly of the entire nuclear receptor complex in the nuclei of living cells. A second part of this project is to use mass spectrometry to identify other members of the PPAR/RXR complex in response to the application of different fatty acid ligands to cells. There are many links between this project and the group of Sander Kersten at Human Nutrition and Epidemiology as well as with the group of Jacques Vervoort (see under Proteins@Work) that deals with estrogen receptors and the isolation of protein complexes.
In plant signal transduction we currently focus on a group of plasma membrane receptors called the Somatic Embryogenesis Receptor-like Kinase family in Arabidopsis thaliana. This family is acting as coreceptors to another class of membrane receptors involved in perceiving brassinosteroids. Brassinosteroids are related in structure to the steroids that regulate many processes in animals. The approaches we use are genetic, by knocking out receptors and seeing what the effect on the development and fertility of Arabidopsis plants is, and biochemical where we are studying interaction between receptors in living plant cells. Also recycling, heterodimerization and in vivo measurement of phosphorylation activity are topics currently addressed. The final aim of this approach is to link observed genetic interactions to with receptor functioning at protein level.