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Signal Transduction

Most of the diseases associated with aging involve defects in proteins involved in cellular regulation. Not surprisingly, the majority of pharmacologically active compounds target signalling proteins. Most of the cytotoxic compounds found in animal venoms and plant toxins specifically affect signal transduction proteins. About 5 percent of the genes in the human genome specify hormones, growth factors and other cytokines involved in cell to cell communications, whereas at least 16 percent specify proteins that transduce signals from these extracellular mediators inside of cells. The discovery of growth factors and other cytokines and the ability to mass-produce recombinant forms of these proteins has spurred the growth of the biotechnology industry for the last three decades. There remains high interest in novel genes that encode secreted proteins for their therapeutic potential. However, intracellular signalling proteins have also commanded the attention of the biopharmaceutical industry over the last decade.

Signalling proteins coordinate the precise orchestration of metabolism and other cellular processes in response to environmental cues.
They operate within obscure networks of thousands of different regulatory proteins. These signal transduction networks link receptors for extracellular mediators at the cell surface to appropriate effector responses throughout the cell. Variants of these networks operate in each of the different types of cells in the human body. Through signalling protein networks, different cells monitor their environment and react appropriately to the benefit of the organism, even if this means that individual cells must commit suicide (a process referred to as apoptosis). Real havoc ensues when critical proteins malfunction as a consequence of mutations in the genes that encode them. Over 400 human diseases have been linked to defects in signal transduction pathways. The importance of signal transduction is underscored by the over one hundred thousand researchers in university, industrial, hospital and government laboratories world-wide that are actively investigating cell regulation. Nevertheless, while many of the components in cell signalling networks have now been identified, our knowledge of the architecture of these networks is very rudimentary. There appears to be over 10 million potential connections in cell signalling networks, but less than 20,000 have been elucidated.