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Science 31 May 2002:
Vol. 296. no. 5573, pp. 1635 - 1636
DOI: 10.1126/science.1071553
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Viewpoint

The Fas Signaling Pathway: More Than a Paradigm

Harald Wajant

Apoptosis and related forms of cell death have central importance in development, homeostasis, tumor surveillance, and the function of the immune system. Apoptosis is initiated by two principal pathways. The intrinsic pathway emerges from mitochondria, whereas the extrinsic pathway is activated by the ligation of death receptors. This Viewpoint introduces the basic mechanisms of the extrinsic pathway, using the example of the prototypical death receptor Fas and its role in apoptosis, but it also points out the increasingly understood importance of this receptor as a non-apoptotic signal transducer.

Institute of Cell Biology and Immunology, Allmandring 31, University of Stuttgart, 70 569 Stuttgart, Germany. E-mail: harald.wajant{at}po.uni-stuttgart.de

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   Abstract »    Full Text »    PDF »
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