P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members
P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members
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DOI：
10.1074/jbc.271.49.31704
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发表时间：
1996-12-06
影响因子：
4.8
通讯作者：
VanEtten, RA
中科院分区：
文献类型：
--
作者：
Ilaria, RL;VanEtten, RA
费城染色体易位的产物P210和p190（BCR/ABL）是细胞质蛋白酪氨酸激酶，其共享将造血细胞依赖性细胞系转化为细胞因子独立性的能力，但在体内诱导的白血病谱中不同。我们已经分析了Bcr/Abl转化的造血细胞中的Janus激酶（JAK）和信号转导子和转录激活子（STAT）通路，STAT 5以及在较小程度上，STAT 1和3在P210和p190（BCR/ABL）转化的细胞中通过酪氨酸磷酸化和诱导DNA结合活性而组成性激活，但P190的不同之处在于它也显著激活STAT 6，在Bcr/Abl转化的细胞中，JAKs 1、2和3的酪氨酸磷酸化水平较低，但与Bcr/Abl没有可检测到的复合物形成，P210对STAT 5的激活没有被两种不同的显性阴性JAK突变体阻断，提示P210和p190（BCR/ABL）基因可能与BCR/ABL基因有关。直接激活特定的STAT家族成员，可能有助于解释它们在白血病发生中重叠但不同的作用。
The products of the Philadelphia chromosome translocation, P210 and p190(BCR/ABL), are cytoplasmic protein tyrosine kinases that share the ability to transform hematopoietic cytokine-dependent cell lines to cytokine independence but differ in the spectrum of leukemia induced in vivo. We have analyzed the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways in hematopoietic cells transformed by Bcr/Abl, STAT5 and, to a lesser extent, STATs 1 and 3 were constitutively activated by tyrosine phosphorylation and induction of DNA binding activity in both P210 and p190(BCR/ABL)-transformed cells, but P190 differed in that it also prominently activated STAT6, There was low level tyrosine phosphorylation of JAKs 1, 2, and 3 in Bcr/Abl-transformed cells, but no detectable complex formation with Bcr/Abl, and activation of STAT5 by P210 was not blocked by two different dominant-negative JAK mutants, These results suggest that P210 and p190(BCR/ABL) directly activate specific STAT family members and may help explain their overlapping yet distinct roles in leukemogenesis.