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The Connections Maps, Science's freely accessible database of information on signal transduction featured at Science's online Signal Transduction Knowledge Environment (STKE), continues to grow. This issue of Science features Viewpoints in which authorities who have constructed new Connections Map pathways provide overviews of the biological and medical processes that are regulated and briefly look ahead to future developments. That signaling mechanisms are shared across distantly related organisms is readily apparent. Alonso and Stepanova (p. 1513) describe signaling by ethylene, a gaseous plant hormone that regulates processes such as seed germination and fruit ripening. Receptors for ethylene are similar to two-component histidine kinases, common signaling machines in bacterial cells. Ethylene signals are also apparently modulated by a mitogen-activated protein kinase (MAPK) cascade, a signaling module present in eukaryotic organisms from yeast to humans. As Gfeller and Farmer describe (p. 1515), the plant immune system is regulated by jasmonates, fatty acid derivatives somewhat like vertebrate prostaglandins. Much remains to be defined in the jasmonate pathways, including the jasmonate receptor.
In other pathways, many components are known and can be connected in complicated networks. Investigation is turning to fascinating questions of how a limited set of similar or even identical components is assembled in different ways in distinct cell types to control completely different biological responses. The MAPK cascade (a series of protein kinases sequentially activated by phosphorylation) also acts in three distinct signaling pathways in yeast: a pheromone sensing pathway (Wang and Dohlman, p. 1508), a pathway that monitors extracellular osmotic conditions (Westfall et al., p. 1511), and a nutrient-sensitive pathway that converts yeast into a connected filamentous form (Truckses et al., p. 1509). These pathways even share one identical member of the MAPK cascade, yet specificity is normally faithfully maintained.
In humans, fibroblast growth factor receptors (FGFRs) and epidermal growth factor receptors (EGFRs) are receptor tyrosine kinases that control cell proliferation and cell death and are implicated in common debilitating diseases (Schlessinger, p. 1506). These receptors share similar signaling machinery (including MAPK cascades), but the components are wired together in distinct ways that may change the amplitude, duration, and localization of signals in the cell. Vivier et al. (p. 1517) describe signaling in deadly lymphocytes known as natural killer cells that provide a first line of defense against infection in mammals. Again, the ubiquitous MAPK cascade crops up. The immunologist's challenge is to understand a system where both stimulatory and inhibitory receptors exist and signals may spread from one to multiple receptors.
Eiden notes in his Editorial (p. 1437) that knowledge management has become critical as efforts proceed to decipher biological regulatory mechanisms and manipulate them for beneficial effect. Mapping the connections and providing enhanced access to information about pathways and components may be the easy part. Using assembled knowledge to decipher how signals vary in time and space, and how subtle differences in network wiring and possible dynamic changes in connectivity produce fine regulation that is robust to all sorts of insults and perturbations, will likely require the best tools we can muster--and then some.
The editors suggest the following Related Resources on Science sites:
In Science Magazine
Lee E. Eiden (26 November 2004) Science306 (5701), 1437.
[DOI: 10.1126/science.1107196] |Summary »|PDF »