| abstract |
The present invention is directed to novel chimeric constitutively active recptor proteins and DNA sequences encoding these proteins. The chimeric receptors comprise a receptor, or functional fragments thereof, operatively fused to a ligand for the receptor, or functional fragments thereof. The receptor and ligand are not normally found associated together and only associate to induce activity of the receptor. By fusing the ligand to the receptor, however, the receptor is capable of constitutive transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of cell-surface receptors and ligands therefor, may be employed in the present invention, wherein the receptors and ligands may be naturally occuring or synthetic. There are also provided nucleic acid constructs, vectors, cells, and transgenic animals which are capable of expressing the chimeric receptors. In addition, there are provided methods for transforming an inducible receptor into a chimeric constitutively active receptor by fusing a ligand therefor to the receptor. In addition, there are provided methods for producing such chimeric receptors, as well as methods for the use thereof, including assays to identify additional ligands for receptors and therapeutic and diagnostic applications. |