磷酸化
融合蛋白
生物
酪氨酸磷酸化
贾纳斯激酶
Janus激酶2
分子生物学
SH2域
细胞生物学
酪氨酸激酶
蛋白激酶结构域
信号转导
癌症研究
生物化学
重组DNA
基因
突变体
作者
Jen M.-Y. Ho,Bryan K. Beattie,Jeremy A. Squire,David A. Frank,Dwayne L. Barber
出处
期刊:Blood
[American Society of Hematology]
日期:1999-06-15
卷期号:93 (12): 4354-4364
被引量:80
标识
DOI:10.1182/blood.v93.12.4354
摘要
Abstract To study constitutive Janus kinase signaling, chimeric proteins were generated between the pointed domain of the etstranscription factor TEL and the cytosolic tyrosine kinase Jak2. The effects of these proteins on interleukin-3 (IL-3)–dependent proliferation of the hematopoietic cell line, Ba/F3, were studied. Fusion of TEL to the functional kinase (JH1) domain of Jak2 resulted in conversion of Ba/F3 cells to factor-independence. Importantly, fusion of TEL to the Jak2 pseudokinase (JH2) domain or a kinase-inactive Jak2 JH1 domain had no effect on IL-3–dependent proliferation of Ba/F3 cells. Active TEL-Jak2 constructs (consisting of either Jak2 JH1 or Jak2 JH2+JH1 domain fusions) were constitutively tyrosine-phosphorylated but did not affect phosphorylation of endogeneous Jak1, Jak2, or Jak3. TEL-Jak2 activation resulted in the constitutive tyrosine phosphorylation of Stat1, Stat3, and Stat5 as determined by detection of phosphorylation using activation-specific antibodies and by binding of each protein to a preferential GAS sequence in electrophoretic mobility shift assays. Elucidation of signaling events downstream of TEL-Jak2 activation may provide insight into the mechanism of leukemogenesis mediated by this oncogenic fusion protein.
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