Abstract: Methods and compositions are provided for modified cells, where a chimeric protein consisting of a ligand binding domain fused to an action domain is employed which initiates a signal which activates a biological process: transcription of at least one gene, usually a second construct introduced into the host cells; exocytosis; or an extracellular process. The second construct optimally present provides for a promoter which responds to a transcriptional activation action domain to provide for transcription, when an appropriate ligand binds to the ligand binding domain. Exemplary of the system is the use of an FKBP/CD3.zeta. or transcription factor fusion protein, using dimeric FK506 or FK520 as the ligand and a promoter responsive to NF-AT or other transcription factor requiring two molecules for transcriptional activation.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
February 16, 1999
Assignees:
Board of Trustees of the Leland Stanford Junior University, President and Fellows of Harvard College
Inventors:
Gerald R. Crabtree, Stuart L. Schreiber, David M. Spencer, Thomas J. Wandless, Peter Belshaw, Steffan Ho