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.
Shen
Xu-Liang
XL
Department of Hematology, Heping Hospital of Changzhi Medical College, Changzhi 046000, China.
Wei
Wu
W
Xu
Hong-Liang
HL
Zhang
Mei-Xiang
MX
Qin
Xiao-Qi
XQ
Shi
Wen-Zhi
WZ
Jiang
Zhi-Ping
ZP
Chen
Yi-Jian
YJ
Chen
Fang-Ping
FP
D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D064249:Securin; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology
D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D050799:STAT5 Transcription Factor; D064249:Securin; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C578002:pituitary tumor-transforming protein 1, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2