Hybrid receptors for efficient assay of modulators of receptor protein-tyrosine kinases

摘要

Hybrid receptors are provided that comprise (a) the extracellular domain of the Ret receptor kinase, containing one or more amino acid residue substitutions, deletions or additions that render it capable of activating an intracellular receptor kinase domain in a ligand-independent manner, and (b) the kinase domain of a heterologous receptor protein kinase. The present invention is also directed to nucleic acids and expression vectors encoding these hybrid receptor proteins, host cells expressing these hybrid receptor proteins, methods for detecting a modulator of receptor protein kinase activity, and membrane preparations comprising recombinantly produced hybrid receptor protein. The hybrid receptors are useful for assays for the determination of modulators of receptor protein kinase activity, being particularly useful in cases where the ligand for the receptor kinase is unknown, or difficult to obtain or use.