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Science 310 (5745): 65-

Copyright © 2005 by the American Association for the Advancement of Science

Signaling: From Stem Cells to Dead Cells

L. Bryan Ray, Nancy R. Gough, Elizabeth M. Adler

This special section on cell signaling features Viewpoints from contributing authorities who have provided annotated signaling pathways for Science's Signal Transduction Knowledge Environment (STKE) Connections Maps database. These overviews provide a snapshot of the current understanding of signaling pathways that influence a broad range of biological processes, from the birth of proliferating stem cells through cellular destruction by apoptosis. Detailed information on the components that make up these pathways, and on their relations with one another, can be viewed in the STKE Connections Map database, a resource available free of charge (with registration) to the entire scientific community through the Web interface at Science's STKE.

Many scientists are optimistic that the manipulation of stem cells will allow marked advances in the treatment of currently intractable diseases. Realizing the promise of these versatile cells will require understanding of their native control mechanisms. Members of the transforming growth factor-beta (TGF-beta) family have emerged as critical regulators of multiple stages in the life of various stem cells (Mishra et al., p. 68). TGF-beta family members initiate signals that can regulate the proliferation of stem cells in an undifferentiated state, specification of or commitment to a particular developmental lineage, and, in some cases, later differentiation into mature cells. Analogous effects of TGF-beta family members on proliferation and differentiation are thought to account for their effects on cancer cells.

Figure 1
CREDIT: S. M. ASSMANN

Many processes in differentiated cells are regulated by ligands that bind to receptors coupled to signal-transducing G proteins (heterotrimeric guanine nucleotide-binding proteins). The vast family of these receptors in mammals is under intense study, in part because many currently prescribed therapeutic agents act by modifying signals from such receptors. Assmann (p. 71) surveys the situation in plants, where so far just one G protein a subunit has been identified (there are more than 20 in humans). She asks whether analysis of the simpler plant systems might provide new insights to investigators of both the plant and animal systems.

Arguably the most serious signal a cell will ever face is one that sends it down the path of organized self-destruction known as apoptosis. Spierings et al. (p. 66) have created a group of large pathways at the STKE Connections Maps that annotate some of the more than 150 components that are implicated in the signals that result in the disruption of mitochondrial function and the activation of caspases (proteases that chew up cellular substrates and lead to cell death). The summary poses the philosophical question of where this regulatory pathway starts and ends--a matter complicated by the fact that many if not all cell functions may contribute to signals that ultimately influence the cell's choice to live or die.



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