Koretzky G A, Picus J, Thomas M L, Weiss A
Department of Medicine, University of California, San Francisco 94143.
Nature. 1990 Jul 5;346(6279):66-8. doi: 10.1038/346066a0.
Stimulation of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase and the generation of phosphatidyl inositol (PtdIns)-derived second messengers. Several reports have indicated that CD45, a haematopoietic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain, is important in lymphocyte activation. To examine the possibility that CD45 might influence proximal signal transduction events through the TCR, we have isolated a variant of the human T-cell leukaemic line, HPB-ALL, which fails to express this phosphatase. Unlike cells expressing CD45, stimulation of the TCR in the CD45-negative cell does not result in PtdIns-derived second messengers. Reconstitution of CD45 expression restored early signalling events through the TCR. To localize the site of CD45 action, the human muscarinic type 1 receptor, which also activates the PtdIns second messenger pathway, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate PtdIns-derived second messengers, there was normal activity of the PtdIns pathway when human muscarinic receptor type 1 was stimulated, despite the absence of CD45. These data indicate that CD45 influences a cellular component that is essential for effective coupling of the TCR to the PtdIns second messenger pathway.
通过T淋巴细胞的抗原受体（T细胞受体；TCR）刺激可导致酪氨酸激酶激活以及磷脂酰肌醇（PtdIns）衍生的第二信使生成。多项报告表明，CD45是一种造血细胞特异性表面糖蛋白，其胞质结构域具有酪氨酸磷酸酶活性，在淋巴细胞激活过程中起重要作用。为了研究CD45是否可能通过TCR影响近端信号转导事件，我们分离出了人T细胞白血病细胞系HPB-ALL的一个变体，该变体无法表达这种磷酸酶。与表达CD45的细胞不同，在CD45阴性细胞中刺激TCR不会产生PtdIns衍生的第二信使。恢复CD45表达可恢复通过TCR的早期信号事件。为了定位CD45的作用位点，将同样激活PtdIns第二信使途径的人毒蕈碱1型受体转染到CD45阴性细胞中。尽管刺激TCR未能产生PtdIns衍生的第二信使，但在刺激人毒蕈碱1型受体时，尽管没有CD45，PtdIns途径仍具有正常活性。这些数据表明，CD45影响一种细胞成分，该成分对于TCR与PtdIns第二信使途径的有效偶联至关重要。
