This week's coordinated special issues of Science and Science's Signal Transduction Knowledge Environment (STKE) (http://www.stke.org/) feature additions to the signaling pathway database at STKE: the Connections Maps.* This database organizes information on the signaling circuitry that regulates cellular function. The Viewpoints in this issue summarize current understanding of how these pathways regulate diverse functions in health and disease. Biochemical signaling pathways interact to form a complicated network that becomes evident when viewing the Connections Maps pathways. “Pathway” units are used for convenience, but new navigational tools allow users to “walk” from one component to another, exploring how the same component works in multiple pathways. “Interpathway connections” show branch points where one pathway influences another [see the Editorial Guide at STKE (www.stke.org/cgi/content/full/sigtrans;2003/186/eg8)].
Viewpoints from Barton and Medzhitov (p. 1524) and Kelly-Welch et al. (p. 1527) discuss signaling by Toll-like receptors and interleukins (ILs). The Toll-like receptors enable the body to detect the presence of microbial invaders and initiate processes that defend against such an attack. Signals mediated by IL-4 and IL-13 present potential therapeutic targets for treatment of asthma and allergies. Xiang and Kobilka (p. 1530) describe signaling by adrenoceptors, which control normal heart function and can contribute to heart failure. Vaudry et al. (p. 1532) address multiple pathways that contribute to life-or-death decisions in cerebellar neurons. Important early in life for proper developmental patterning, these pathways may later malfunction in neurodegenerative diseases.
Similar circuits can be constructed from different components, as Van Gelder (p. 1534) describes for pathways that make up biological clocks. Some surprises come from the huge family of receptors that couple to heterotrimeric guanine nucleotide-binding proteins (G proteins). Kimmel and Parent (p. 1525) describe a receptor in the social ameoba Dictyostelium that signals through a G protein but also triggers G protein-independent signals. This model organism provides a system for understanding how cells orient themselves in very shallow gradients of chemoattractants. Wang and Malbon (p. 1529) describe a receptor that has structural characteristics of a G protein-coupled receptor but is best understood to signal by a different mechanism. The authors summarize evidence that these receptors (“Frizzleds”) may also use a traditional G protein activation mechanism.
We hope the Viewpoints lead you to explore the Connections Maps at Science's STKE. We anticipate that a comprehensive signaling database will enable analysis not previously possible with information stored in the text of traditional research publications.
↵*Access to the Connections Maps is free to registered users. Full-text features require an individual or institutional subscription.