B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription (STAT)1 and STAT3 constitutively phosphorylated on serine residues
B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription (STAT)1 and STAT3 constitutively phosphorylated on serine residues
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DOI：
10.1172/jci119869
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发表时间：
1997-12-15
影响因子：
15.9
通讯作者：
Ritz, J
中科院分区：
文献类型：
--
作者：
Frank, DA;Mahajan, S;Ritz, J
为了探讨慢性淋巴细胞白血病（CLL）的发病机制，我们检测了CLL患者细胞中一种或多种信号转导和转录激活因子（STAT）的磷酸化是否异常，在CLL细胞中没有检测到任何STAT的组成性酪氨酸磷酸化，为了评估CLL细胞中STAT 1和STAT 3的丝氨酸残基的磷酸化，我们提出了特异性识别在ser-727上磷酸化的STAT 1形式和在ser-727上磷酸化的STAT 3形式的抗体。我们发现在100%的CLL患者（n = 32）中，STAT 1和STAT 3在丝氨酸上组成性磷酸化，这与正常外周血B淋巴细胞或从扁桃体分离的CD 5（+）B细胞相反，在正常外周血B淋巴细胞或CD 5（+）B细胞中不存在这种磷酸化，在其他白血病中偶尔观察到STAT 1和STAT 3的丝氨酸磷酸化，但这仅在CLL中是普遍发现。这些STAT的丝氨酸磷酸化是一个连续的过程，因为CLL细胞与激酶抑制剂H7的孵育导致这些丝氨酸残基的去磷酸化。CLL细胞中的STAT丝氨酸激酶尚未被鉴定，并且似乎既不是促分裂原活化蛋白激酶也不是pp 70（s6 k）。STAT 1和STAT 3的组成型丝氨酸磷酸化存在于迄今为止测试的所有CLL样品中，尽管该修饰的生理学意义仍有待确定。
To explore the pathogenesis of chronic lymphocytic leukemia (CLL), we examined whether phosphorylation of one or more signal transducer and activator of transcription (STAT) factors was abnormal in cells from CLL patients, No constitutive tyrosine phosphorylation was detected on any STAT in CLL cells, To assess the phosphorylation of serine residues of STAT1 and STAT3 in CLL cells, we raised antibodies that specifically recognize the form of STAT1 phosphorylated on ser-727 and the form of STAT3 phosphorylated on ser-727, We found that in 100% of patients with CLL (n = 32), STAT1 and STAT3 were constitutively phosphorylated on serine, This was in contrast to normal peripheral blood B lymphocytes or CD5(+) B cells isolated from tonsils, in which this phosphorylation was absent, Serine phosphorylation of STAT1 and STAT3 was seen occasionally in other leukemias, but it was a universal finding only in CLL. The serine phosphorylation of these STATs was a continuous process, as incubation of CLL cells with the kinase inhibitor H7 led to the dephosphorylation of these serine residues, The STAT serine kinase in CLL cells has not been identified, and appears to be neither mitogen-activated protein kinase nor pp70(s6k), In summary, the constitutive serine phosphorylation of STAT1 and STAT3 is present in all CLL samples tested to date, although the physiologic significance of this modification remains to be determined.