A Signal Transduction Database

Abstract

We are developing a signal transduction database which represents molecular interactions involved in the signaling pathways in a cell from the activation of cell surface receptors by external signals to the activation of transcription factors in the nucleus. The database is linked to the Medline literature, the SWISS-PROT and PIR protein sequence database, the PDB protein 3-D structural database, the LIGAND chemical database for enzyme reactions, and the OMIM database on genetic diseases. We provide a graphical user interface of the World Wide Web (WWW) to access this database. The signal transduction from extracellular signals to gene expression is one of the signi cant cellular events that are beginning to be unraveled in molecular details. The event starts at the cell surface receptor accepting an external signal. The signal is transmitted inside the cell to key signaling molecules such as Ras and G-protein. The activation of these molecules is often followed by a cascade of protein phosphorylation events which results in the activation of speci c transcription factors in the cell nucleus. Such an overall picture is derived from numerous experiments on molecular interactions, i.e., data on one molecule a ecting other molecules either directly or indirectly. Our long-term objective is to automatically construct such an overall picture from pieces of data stored in the database. Toward that end we have started collecting data on molecular interactions that play parts in the signal transduction pathways and experimenting various representations and manipulations of those data. Our short-term objective is to provide a browser of di erent types of data in an integrated environment. Thus, the molecular interaction data are linked to consensus views of the transduction pathways, as well as to other databases including bibliographic data (Medline), protein sequences (SWISS-PROT and PIR), protein 3-D strctures (PDB), chemical compounds Naf -â« I O u 3eâQOQo m 611 3eidj=-V4 in enzyme reactions (LIGAND), and genetic diseases (OMIM). Table 1 shows a description of molecular interactions in the Ras pathway, where the basic element is a pair of interacting molecules or molecular complexes, called a donor and an acceptor, together with the description of molecular events. The interface to access our signal transduction database is implemented using Mosaic in the World Wide Web (WWW) system, since Mosaic has an easy-to-use graphical user interface and also since we already have an integrated retrieval system called WebDBget linking fteen databases in molecular biology (Y. Akiyama and M. Kanehisa, unpublished). Data items in Table 1 can be clickable by mouse operations to retrieve related information.