Interleukin 7 receptor ligation stimulates tyrosine phosphorylation, inositol phospholipid turnover, and clonal proliferation of human B-cell precursors.
Interleukin 7 receptor ligation stimulates tyrosine phosphorylation, inositol phospholipid turnover, and clonal proliferation of human B-cell precursors.
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白细胞介素 7 受体连接刺激酪氨酸磷酸化、肌醇磷脂周转和人类 B 细胞前体的克隆增殖。
DOI：
10.1073/pnas.88.9.3589
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发表时间：
1991
影响因子：
11.1
通讯作者：
Ledbetter,JA
中科院分区：
文献类型：
--
作者：
Uckun,FM;Dibirdik,I;Smith,R;Tuel-Ahlgren,L;Chandan-Langlie,M;Schieven,GL;Waddick,KG;Hanson,M;Ledbetter,JA
功能性白介素 7 (IL-7) 受体在具有种系免疫球蛋白重链基因的多表型、双表型和未成熟 B 系人淋巴前体细胞表面表达，但在具有重排和/或表达免疫球蛋白重链基因的更成熟 B 系淋巴细胞上不表达。因此，IL-7 在人类 B 细胞个体发育的最早阶段可能具有重要的调节作用。未成熟 B 细胞前体细胞上的表面 IL-7 受体与重组人 IL-7 (rhIL-7) 的结合导致多种磷蛋白的酪氨酸磷酸化增强，刺激肌醇磷脂周转和 DNA 合成，并促进其克隆增殖。这些作用是 (i) rhIL-7 特异的，因为 rhIL-3、rhIL-4、rhIL-5、rhIL-6 和重组人粒细胞集落刺激因子不会对 IL-7 受体阳性人 pro-B 细胞产生类似的活性； (ii) 由 IL-7 受体介导，因为在 IL-7 受体阴性的 B 系淋巴细胞群中未观察到它们。 rhIL-7 诱导的 35-、53-、55-、62-、69-、76-、94-、150-、170-和 190-kDa 底物上的酪氨酸磷酸化以及 rhIL-7 诱导的肌醇磷脂周转刺激均被酪氨酸激酶抑制剂金雀异黄酮消除。这些结果表明，未成熟的人 B 细胞前体群体上的 IL-7 受体与功能性酪氨酸激酶途径密切相关，并且酪氨酸磷酸化是产生 IL-7 受体相关跨膜信号的重要且可能是强制性的步骤。
Functional interleukin 7 (IL-7) receptors are expressed on the surface of multiphenotypic, biphenotypic, and immature B-lineage human lymphoid precursor cells with germ-line immunoglobulin heavy-chain genes but not on more mature B-lineage lymphoid cells with rearranged and/or expressed immunoglobulin heavy-chain genes. Thus, IL-7 may have an important regulatory role during the earliest stages of human B-cell ontogeny. The engagement of the surface IL-7 receptors on immature B-cell precursor cells with recombinant human IL-7 (rhIL-7) results in enhanced tyrosine phosphorylation of multiple phosphoproteins, stimulates inositol phospholipid turnover and DNA synthesis, and promotes their clonal proliferation. These effects are (i) specific for rhIL-7, since rhIL-3, rhIL-4, rhIL-5, rhIL-6, and recombinant human granulocyte colony-stimulating factor do not elicit similar activities on IL-7 receptor-positive human pro-B cells; and (ii) mediated by IL-7 receptors, since they are not observed in IL-7 receptor-negative B-lineage lymphoid cell populations. rhIL-7-induced tyrosine phosphorylation on the 35-, 53-, 55-, 62-, 69-, 76-, 94-, 150-, 170-, and 190-kDa substrates as well as rhIL-7-induced stimulation of inositol phospholipid turnover are abrogated by the tyrosine kinase inhibitor genistein. These results demonstrate that the IL-7 receptor on immature human B-cell precursor populations is intimately linked to a functional tyrosine kinase pathway and tyrosine phosphorylation is an important and perhaps mandatory step in the generation of the IL-7 receptor-linked transmembrane signal.