Dual activity kinase domains and uses thereof

摘要

The present invention relates to a dual activity domain of JAK proteins, namely JH2. It is provided that the JH2 domain is a true and important target for drug development, especially for diseases caused by aberrant JAK signalling, such as myeloproliferative disorders and leukemias.

主权项

1. An assay for screening and identifying a modulator of JH2 kinase activity, comprising:
a) reacting a test substance with a reaction mixture comprising a JH2 domain, ATP or an analog thereof, divalent cations, and optionally, a substrate for the kinase activity of JH2, and b) determining in said reaction mixture of step 1) at least one feature selected from the group consisting of JH2 autophosphorylation, substrate phosphorylation, binding of ATP or an analog thereof to the JH2 domain, binding of the test substance to the JH2 domain, binding of the substrate to the JH2 domain, ADP production, and a conformational or structural state of JH2, and c) identifying said test substance as a modulator of JH2 kinase activity if the feature determined in step b) is different from the corresponding feature determined in the absence of said test substance.