Hematopoietic Cell Phosphatase Is Recruited to CD22 following B Cell Antigen Receptor Ligation (*)

Hematopoietic Cell Phosphatase Is Recruited to CD22 following B Cell Antigen Receptor Ligation (*)
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B 细胞抗原受体连接后,造血细胞磷酸酶被招募至 CD22 (*)

DOI:
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发表时间:
1995
影响因子:
4.8
通讯作者:
R. V. van Lier
R. V. van Lier
中科院分区:
生物学2区
文献类型:
--
作者:
A. Lankester;G. V. van Schijndel;R. V. van Lier

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造血细胞磷酸酶是一种非受体蛋白酪氨酸磷酸酶,在造血细胞系中优先表达。缺乏(功能性)造血细胞磷酸酶的母鼠,在调节B细胞活化和分化方面有严重的紊乱。由于已知通过B细胞抗原受体传递的信号指导这些过程,我们决定分析造血细胞磷酸酶和B细胞抗原受体之间的分子相互作用。B细胞抗原受体的连接诱导造血细胞磷酸酶的适度酪氨酸磷酸化,并形成含有额外的68-70-和135 kDa磷酸蛋白的多分子复合体。在静息的B细胞中,大多数造血细胞磷酸酶蛋白存在于胞浆中,而在B细胞抗原受体交联后,一小部分移位到膜上,在那里它特异性地与135 kDa的磷酸蛋白结合。这个135 kDa的糖蛋白被鉴定为CD22,它是B细胞抗原受体复合体的跨膜结合蛋白。综上所述,这些发现首次提供了胞浆酪氨酸磷酸酶参与抗原受体介导的B细胞活化的直接证据,表明在体内B细胞抗原受体成分或相关分子可能是其催化活性的底物。
Hematopoietic cell phosphatase is a nonreceptor protein tyrosine phosphatase that is preferentially expressed in hematopoietic cell lineages. Motheaten mice, which are devoid of (functional) hematopoietic cell phosphatase, have severe disturbances in the regulation of B cell activation and differentiation. Because signals transduced via the B cell antigen receptor are known to guide these processes, we decided to analyze molecular interactions between the hematopoietic cell phosphatase and the B cell antigen receptor. Ligation of the B cell antigen receptor induces moderate tyrosine phosphorylation of hematopoietic cell phosphatase and the formation of a multimolecular complex containing additional 68-70- and 135-kDa phosphoproteins. In resting B cells most of the hematopoietic cell phosphatase proteins reside in the cytosolic compartment, whereas after B cell antigen receptor cross-linking, a small fraction translocates toward the membrane where it specifically binds to the 135-kDa phosphoprotein. This 135-kDa glycoprotein was identified as CD22, a transmembrane associate of the B cell antigen receptor complex. Together these findings provide the first direct evidence that this cytoplasmic tyrosine phosphatase is involved in antigen receptor-mediated B cell activation, suggesting that in vivo B cell antigen receptor constituents or associated molecules may serve as substrate for its catalytic activity.
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