ANTIIMMUNOGLOBULIN STIMULATION OF LYMPHOCYTES-B ACTIVATES SRC-RELATED PROTEIN-TYROSINE KINASES

ANTIIMMUNOGLOBULIN STIMULATION OF LYMPHOCYTES-B ACTIVATES SRC-RELATED PROTEIN-TYROSINE KINASES
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DOI:
10.1073/pnas.88.16.7410
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发表时间:
1991-08-01
影响因子:
11.1
通讯作者:
MOND, JJ
MOND, JJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BURKHARDT, AL;BRUNSWICK, M;MOND, JJ

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用表面免疫球蛋白(sIgD或sIgM)抗体刺激静息B淋巴细胞可诱导蛋白酪氨酸磷酸化,这涉及一种或多种B细胞蛋白酪氨酸激酶(PTK)参与sIg信号转导。我们已经评估了src家族的PTK成员是否参与了这一过程。我们的研究结果表明,添加抗体IgD或IgM可以刺激PTK活性的blk,fyn和林恩基因产物。此外,发现所有三种PTK均与静息B细胞洋地黄皂苷裂解物中的sIg发生免疫共沉淀。在所有的刺激条件下,无论是通过sIgD或sIgM启动,blk基因产物p56blk显示最强的激活指数。这些激酶,特别是p56 blk的活化动力学,抑制了新酪氨酸磷酸化B细胞蛋白的早期出现,表明这组激酶可能是sIg活化B细胞中酪氨酸激酶活性的一部分。这些观察结果表明,src家族成员的PTK和B细胞抗原受体之间的功能和可能的物理关联。
Stimulation of resting B lymphocytes with antibodies to surface immunoglobulin (sIgD or sIgM) induces protein tyrosine phosphorylation, implicating one or more B-cell protein-tyrosine kinases (PTKs) in sIg signal transduction. We have evaluated whether members of the src family of PTKs are involved in this process. Our results show that addition of antibodies to IgD or to IgM can stimulate the PTK activity of the blk, fyn, and lyn gene products. Additionally, all three PTKs were found to coimmunoprecipitate with sIg in digitonin lysates from resting B cells. In all stimulatory conditions, whether initiated through sIgD or sIgM, the blk gene product p56blk displayed the strongest activation index. The kinetics of activation of these kinases, particularly that of p56blk, paralleled the early appearance of newly tyrosine-phosphorylated B-cell proteins, suggesting that this group of kinases may account for some portion of the tyrosine kinase activity in sIg-activated B cells. These observations demonstrate a functional and possible physical association between the members of the src family of PTKs and the B-cell antigen receptor.