Cell signaling mechanisms often transmit information via protein modifications, most importantly the reversible attachment of phosphate, the so-called protein phosphorylation. Researchers at the Max Planck Institute of Biochemistry in Martinsried have now developed a technology to identify and quantify the specific sites in proteins that get phosphorylated in answer to certain stimuli in living cells. Under the lead of Matthias Mann, the scientists found 6,600 phosphorylation sites - 90 percent of which were unknown - in 2,244 proteins and observed their temporal dynamics. All these phosphorylation sites are now listed in the newly created Phosida database to make them available for efficient use by scientists working in different areas, among them tumour researchers: Defects in cellular signaling often occur in many types of cancer (Cell, November 2, 2006).
The mammalian cell constantly receives signals from its surroundings to which it has to respond appropriately. Growth factors, for example, can lead to growth of a cell, its differentiation or proliferation. Defects in these tightly regulated and controlled processes can cause cancer and other human diseases. In recent decades, knowledge of the important players in signal transduction has been painstakingly accumulated, mainly through the study of individual molecules in specific pathways. This approach may fall short though, because the cellular answer to environmental stimuli often doesn't show on the level of production but the modification of proteins after their synthesis. "Phosphorylation is the most important and most thoroughly researched modification," says Mann. "An estimated one-third of all cellular proteins are affected. Therefore, the dynamic phosphoproteome provides a missing link in a global, integrative view of cellular regulation."