**7. Making up a signalling system**

56 Biomedical Science, Engineering and Technology

In the discussion above it was argued that instruments may be similar but unique. However, there are often quite diverse instruments which share common mechanisms or structures. In signalling many proteins may also share common structures, with those structures having similar roles within the protein. A good example here is the EF hand (Lewitt-Bentley & Rety, 2000), which binds and causes a conformational change in a protein in response to changes in the levels of calcium ions in cells. EF hands can be found in a calcium controlled kinases which are able to phosphorylate downstream proteins, but EF hands are found in a wide range of other proteins too, for example the DUOX proteins involved in reactive oxygen species metabolism (Lambeth *et al*., 2007). Although there might be subtle differences in the EF hands in different proteins the structural domain is still identifiable as being an EF hand, having the same basic function but being involved in a proteins which when taken as a

Fig. 5. cAMP and cGMP pathways are very similar. As well as cAMP and cGMP having very similar structures, if drawn in a simplistic view as shown here the signalling pathways in which they are involved is also very similar. Both are produced by cyclases, both are perceived by protein kinase, and in fact both are removed by phosphodiesterases. Both can have other effects and if viewed in more detail there are significant differences in their pathways. Importantly, cAMP and cGMP are involved in specific signalling, despite the similarities. PKA: cAMP-dependent protein kinase; PKG: cGMP-dependent protein kinase. Therefore many signalling proteins have domains which are similar to each other and to continue our analogy musical instruments are often the same. An idea is repeated, but perhaps has a slightly different role. Consider keyboards on pianos and organs. The idea of having a set of keys which can be pressed can be found on a whole range of instruments, including different types of piano, electric keyboards, organs, harpsichords, accordions, melodicas and many others. Beyond the keyboard the mechanisms may be very different. A piano uses hammers to strike the strings, an organ opens valves to control air into pipes and so on. But the keyboard is a common feature or common structure, like the domain of a protein. And just like the EF hands discussed above, the keyboards in these different instruments may be subtly different, but they are still recognisable as being keyboards despite the overall instruments

being quite different, both in shape and the type of music they play.

**6. Domains and common features** 

whole have different functions in the cell.

Cells in an organism have the same genetic background, that is, they contain the same genome. The genome will encode for all the proteins which are possible to make in that organism, but different cells will have their own unique complement of proteins. Some cells will express genes for a particular signalling pathway, and others won't, perhaps having a different set of signalling proteins. Some cells will need receptors for a selection of hormones or cytokines, but other cells will have no requirement for the recognition of those extracellular signals and therefore will not express those receptors.

In music the genome is perhaps all the instruments that would be available to someone who wishes to form a group of musicians. There is a vast array of instruments available in, for example, the UK and this could be seen as the "music genome" for that country. The "music genome" for perhaps China or a Far East country may contain other instruments not commonly found in the West. So where ever a person is based to create a group of musicians they will have a "genome" to draw from, just as the cell has a genome containing the genes encoding cell signalling components to draw from. Different places could be viewed like different organisms, having different genomes, although often related. But no cell, and no music producer, would wish to enlist all the possible players. An orchestra conductor will take a wide range of instruments, from violins to kettle drums. A pop group producer may take a couple of guitars and a set of drums and little else. It is the vast array of possibilities that allow a cell to tailor its complement of proteins to allow the signalling that it needs, just as a music group will tailor its array of instruments to create the sound it requires. The cell will be able to respond to a particular group of extracellular signals while the leader of a group of musicians will be able to play a specific selection of music.
