TYROSINE PHOSPHATASE CD45 IS ESSENTIAL FOR COUPLING T-CELL ANTIGEN RECEPTOR TO THE PHOSPHATIDYL INOSITOL PATHWAY
TYROSINE PHOSPHATASE CD45 IS ESSENTIAL FOR COUPLING T-CELL ANTIGEN RECEPTOR TO THE PHOSPHATIDYL INOSITOL PATHWAY
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DOI：
10.1038/346066a0
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发表时间：
1990-07-05
期刊：
影响因子：
64.8
通讯作者：
WEISS, A
中科院分区：
文献类型：
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作者：
KORETZKY, GA;PICUS, J;WEISS, A
通过T淋巴细胞的抗原受体（T细胞受体；TCR）刺激T淋巴细胞导致酪氨酸激酶的激活e1,2和产生磷脂酰肌醇（PtdIns）衍生的第二信使3 - 5。一些报道表明，CD45是一种造血细胞特异性表面糖蛋白，其细胞质结构域6 - 10具有酪氨酸磷酸酶活性，在淋巴细胞活化中起重要作用11 - 14。为了研究CD45可能通过TCR影响近端信号转导事件的可能性，我们分离了一种不能表达这种磷酸酶的人类t细胞白血病系hhb - all的变体。与表达CD45的细胞不同，刺激CD45阴性细胞中的TCR不会产生ptdin衍生的第二信使。CD45表达的重建通过TCR恢复了早期信号事件。为了定位CD45的作用位点，将同样激活Ptdlns第二信使通路的人毒蕈碱1型受体15,16转染到CD45阴性细胞中。尽管刺激TCR不能产生ptdln衍生的第二信使，但当刺激人毒蕈碱受体1型时，尽管缺乏CD45， PtdIns通路仍有正常活性。这些数据表明，CD45影响一种细胞成分，这种成分对于TCR与PtdIns第二信使通路的有效偶联至关重要。
STIMULATION of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase1,2and the generation of phosphatidyl inositol (PtdIns)-derived second messengers3–5. Several reports have indicated that CD45, a haematopoetic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain6–10, is important in lymphocyte activation11–14. 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 Ptdlns second messenger pathway15,16, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate Ptdlns-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.