Lankester A C, van Schijndel G M, van Lier R A
Central Laboratory of the Blood Transfusion Service, The Netherlands Red Cross, University of Amsterdam.
J Biol Chem. 1995 Sep 1;270(35):20305-8. doi: 10.1074/jbc.270.35.20305.
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 multi-molecular 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.
造血细胞磷酸酶是一种非受体蛋白酪氨酸磷酸酶，在造血细胞谱系中优先表达。缺乏（功能性）造血细胞磷酸酶的莫特海文小鼠在B细胞活化和分化的调节方面存在严重紊乱。由于已知通过B细胞抗原受体转导的信号可指导这些过程，我们决定分析造血细胞磷酸酶与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发生适度的酪氨酸磷酸化，并形成包含另外68 - 70 kDa和135 kDa磷蛋白的多分子复合物。在静息B细胞中，大多数造血细胞磷酸酶蛋白位于胞质区室，而在B细胞抗原受体交联后，一小部分会向膜移位，在那里它特异性结合135 kDa的磷蛋白。这种135 kDa的糖蛋白被鉴定为CD22，它是B细胞抗原受体复合物的跨膜结合蛋白。这些发现共同提供了首个直接证据，表明这种细胞质酪氨酸磷酸酶参与抗原受体介导的B细胞活化，提示在体内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。
