Kinetic Study of Human Full-Length Wild-Type JAK2 and V617F Mutant Proteins

The Janus kinase 2 (JAK2) is a drug target in particular because a missense mutation in this gene (V617F) has been identified in various human diseases. We report here the first kinetic study of the human full-length wild type and V617F JAK2 proteins and of their isolated kinase domain. The kinetic parameters of both full-length proteins are similar revealing that the mutation does not affect JAK2 catalytic activity suggesting that it has a more complex role in the regulation of JAK2 activity. Our study also shows that the domains located outside the kinase domain have little influence on JAK2 catalytical activity.