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Science 12 November 1993:
Vol. 262. no. 5136, pp. 1019 - 1024
DOI: 10.1126/science.7694365
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Articles

Science, Vol 262, Issue 5136, 1019-1024
Copyright © 1993 by American Association for the Advancement of Science

articles

Controlling signal transduction with synthetic ligands

DM Spencer, TJ Wandless, SL Schreiber, and GR Crabtree

Howard Hughes Medical Institute, Stanford University, CA 94305.

Dimerization and oligomerization are general biological control mechanisms contributing to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. Cell permeable, synthetic ligands were devised that can be used to control the intracellular oligomerization of specific proteins. To demonstrate their utility, these ligands were used to induce intracellular oligomerization of cell surface receptors that lacked their transmembrane and extracellular regions but contained intracellular signaling domains. Addition of these ligands to cells in culture resulted in signal transmission and specific target gene activation. Monomeric forms of the ligands blocked the pathway. This method of ligand-regulated activation and termination of signaling pathways has the potential to be applied wherever precise control of a signal transduction pathway is desired.


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Science 280, 708-711
   Abstract »    Full Text »
Synthetic activation of caspases: Artificial death switches.
R. A. MacCorkle, K. W. Freeman, and D. M. Spencer (1998)
PNAS 95, 3655-3660
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