Animation showing the Jak-Stat signalling pathway mechanism

The Jak-Stat pathway has recently attracted researchers’ attention. This has been motivated by the fact that this pathway is a potential target of future agents for the treatment of myeloproliferative disorders such as: polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

The animation below depicts the Jak-Stat signalling pathway mechanism:

As mentioned above, there are some expectations on the future of JAK STAT pathway in pharmacology:

JAK2 Inhibitors

Despite the success of imatinib mesylate in the treatment of CML, the genetic basis of the other major myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis) has, until recently, remained obscure. It is now apparent that a common activating mutation in JAK2 (V617F) underlies the aberrant signaling and proliferation in most cases, although how one mutation leads to this spectrum of disorders remains unclear. The V617F mutation is found in the pseudokinase domain of JAK2, and disruption of this autoinhibitory region leads to unchecked activity of the kinase. Cells containing the JAK2 V617F mutation are growth inhibited and undergo apoptosis in response to specific JAK2 inhibitors in vitro. Thus, JAK2 inhibitors are under development for the treatment of polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Source: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: D. Golan et al. LWW. 2007

Related links

Series Introduction: JAK-STAT signaling in human disease. Christian W. Schindler. J. Clin. Invest. 109(9): 1133-1137 (2002)

JAK-STAT signaling in asthma. Alessandra B. Pernis and Paul B. Rothman. J. Clin. Invest. 109(10): 1279-1283 (2002)

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