Analysis of signal transduction of Polycythemia vera-associated JAK2 V617F mutant

酪氨酸激酶JAK2 （V617F）的组成性激活突变在真性红细胞增多症的大多数患者中被发现。我们发现JAK2突变体通过异常激活STAT5诱导转化。有趣的是，我们发现JAK2突变体显著诱导了极光激酶A的表达和Akt的激活。我们发现极光激酶A对于JAK2突变体诱导的顺铂诱导的DNA损伤抗性至关重要。此外，我们阐明Akt激活诱导抗凋亡蛋白下调，从而导致抗凋亡活性。

The constitutively activated mutation of tyrosine kinase JAK2 (V617F) is found in the majority of the patients with polycythemia vera. We found that JAK2 mutant induces transformation through aberrant activation of STAT5. Interestingly, it was found that the expression of Aurora kinase A and activation of Akt were significantly induced by JAK2 mutant. We showed that Aurora kinase A was critical for JAK2 mutant-induced resistance to cisplatin-induced DNA damage. Furthermore, we clarified that Akt activation induced the downregulation of anti-apoptotic proteins, leading to anti-apoptotic activity.