Making sense of the human genome: researchers characterize a crucial family of signaling proteins in the human genome


In this month’s Genome Biology, Mitch Kostich and colleagues from the Schering-Plough Research Institute (NJ, USA) have identified and mapped an important group of molecules known as protein kinases. These molecules are central to the communication of information both within and between cells, in a process known as cell signaling. Defective protein kinases are associated with hundreds of human diseases, including some types of cancer, and it is hoped that this map, which shows the relationships between 510 human protein kinases, will help researchers find new drugs that can specifically target diseases caused by a defective protein kinase, as well as unlocking the secrets of 60 previously unidentified members of this family.

If our bodies are to work properly, it is important that cells are doing the right thing at the right time. To get things right, the human body has evolved complex signaling pathways that allow our molecules to communicate with each other. Protein kinases are a central part of many signaling pathways, helping to regulate virtually every function in human cells. They belong to a class of biological molecules known as enzymes, which help all the chemical reactions in our bodies to go according to plan. All protein kinases carry out the same function: they transfer a cluster of atoms, known as a phosphoryl group between different molecules. The movement of a phosphoryl group is similar to the flick of a switch that causes a biochemical pathway go slower or faster.

Kostich and his colleagues searched the publicly available sequence databases to find sequences with similarity to known protein kinase molecules. After removals of duplicates and pseudogenes (genes that are not used), they found 510 sequences that were similar to known protein kinases, of which 60 were previously unidentified. Confident that all 510 sequences coded for protein kinases, they constructed a tree-like diagram known as a phenogram, which maps the relationship between different protein kinases based on the differences in their sequence. This phenogram shows that there are five distinct protein kinase families, a result that is consistent with classification systems based on the functions of different protein kinases.

Understanding the relationships between different members of the protein kinase family in humans will provide researchers with important information to unravel the connections been the structure of a protein kinase and its function. The comprehensive nature of the study will also aid researchers in the design of drugs to help those suffering from disease involving defects in cell signaling. In addition, the study has uncovered 60 new protein kinases for which functions have yet to be assigned.

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