Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells
Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells
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DOI：
10.1038/sj.leu.2400832
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发表时间：
1997-11
期刊：
影响因子：
11.4
通讯作者：
M. Sémichon;H. Merle-Béral;V. Lang;G. Bismuth
中科院分区：
文献类型：
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作者：
M. Sémichon;H. Merle-Béral;V. Lang;G. Bismuth
在慢性淋巴细胞白血病（CLL）期间积聚的B细胞的一个特征是它们对B细胞受体（BCR）刺激的高度异质性功能应答。反应极差的白血病B细胞对许多底物（尤其是磷脂酶C（PLC）γ）的快速酪氨酸磷酸化存在缺陷，以及对BCR刺激的钙升高存在缺陷。这表明BCR相关蛋白酪氨酸激酶（PTK）存在缺陷。我们研究了Syk（一种在BCR与下游信号事件偶联中起关键作用的PTK）的缺陷是否可以解释这些改变。在对抗μ刺激具有低钙应答的B-CLL细胞中，BCR连接触发的Syk酪氨酸磷酸化严重受损。Syk相关性也有缺陷，因为与PLCγ-2共迁移的Syk相关145 kDa蛋白的伴随酪氨酸磷酸化仅在响应的B-CLL细胞中检测到。相比之下，我们发现无论B-CLL细胞反应性如何，激酶的表达相似。这些结果与某些B-CLL细胞中非常近端的BCR信号传导元件不能与由酪氨酸磷酸化和Syk PTK的潜在对接功能主导的下游生化事件连接的可能性一致。
One characteristic of B cells that accumulate during chronic lymphocytic leukemia (CLL) is their highly heterogeneous functional responses to B cell receptor (BCR) stimulation. Leukemic B cells with very poor responses have defective rapid tyrosine phosphorylation of numerous substrates, especially phospholipase C (PLC) γ, as well as a defective calcium elevation on BCR stimulation. This points to a defect in BCR-associated protein tyrosine kinase (PTK). We investigated whether a defect in Syk, a PTK that is pivotal in coupling BCR to downstream signaling events, could account for these alterations. Syk tyrosine phosphorylation triggered by BCR ligation was severely impaired in B-CLL cells with low calcium responses to anti-μ stimulation. Syk associations were also defective, as concomitant tyrosine phosphorylation of a Syk-associated 145 kDa protein comigrating with PLCγ-2 was only detected in responding B-CLL cells. By contrast, we found similar expression of the kinase regardless of B-CLL cell responsiveness. These results are consistent with the possibility that very proximal BCR signaling elements in some B-CLL cells are unable to connect with downstream biochemical events dominated by tyrosine phosphorylation and the potential docking function of Syk PTK.