JAK2V617F/STAT5 signaling pathway promotes cell proliferation through activation of Pituitary Tumor Transforming Gene 1 expression

Gain-of-function mutations of JAK2 play crucial roles in the development of myeloproliferative neoplasms; however, the underlying downstream events of this activated signaling pathway are not fully understood. Our experiment was designed and performed to address one aspect of this issue. Here we report that AG490, a potent JAK2V617F kinase inhibitor, effectively inhibits the proliferation of HEL cells. Interestingly, AG490 also decreases the expression of PTTG1, a possible target gene of the aberrant signaling pathway, in a dose- and time-dependent manner. Furthermore, the promoter activity analyses reveal that the inhibition of the PTTG1 expression is affected at the transcriptional level. Thus, our results suggest that the JAK2V617F/STAT5 signaling pathway promotes cell proliferation through the transcriptional activation of PTTG1.

Research highlights
► AG490, a member of tyrosine kinase inhibitors, could inhibit the JAK2V617F/STAT5 signaling pathway in HEL cell which harbor JAK2V617F mutation.
► Inhibition of the JAK2V617F/STAT5 signaling pathway inhibited the growth of HEL cells.
► JAK2V617F mutation promotes cell proliferation through activation of PTTG1 expression.
► JAK2V617F/STAT5 signaling pathway regulate PTTG1 expression at transcriptional level.