APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation
APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation
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DOI：
10.1016/j.bbrc.2005.03.073
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发表时间：
2005-05-13
影响因子：
3.1
通讯作者：
Takaki, S
中科院分区：
文献类型：
--
作者：
Iseki, M;Kubo-Akashi, C;Takaki, S
含有 PH 和 SH2 结构域的接头分子 (APS) 是一种细胞内接头蛋白，与 Lnk 和 SH2-B 一起构成接头家族的一部分。 APS 转录物在多种组织中表达，包括脑、肾和肌肉以及脾 B 细胞，但在 T 细胞中不表达。我们通过生成在淋巴细胞中过度表达 APS 的 APS 转基因 (APS-Tg) 小鼠，研究了 APS 在 B 细胞发育和激活中的功能。 APS-Tg 小鼠腹膜腔中的 B-1 细胞数量减少，脾脏中的 B-2 细胞数量也减少。在从大前 B 细胞增殖到小前 B 细胞的过渡阶段，骨髓中的 B 细胞发育受到部分损害。在 APS-Tg 小鼠中，由 B 细胞受体 (BCR) 交联而非其他 B 细胞有丝分裂原诱导的 B 细胞增殖也受到损害。 APS 与 BCR 复合物和丝状肌动蛋白共定位于激活的 APS-Tg B 细胞中。因此，APS 似乎在 BCR 信号传导、肌动蛋白重组途径和 B 谱系细胞区室大小的控制中发挥新的负调节作用。 (c) 2005 Elsevier Inc. 保留所有权利。
Adaptor molecule containing PH and SH2 domains (APS) is an intracellular adaptor protein that forms part of an adaptor family along with Lnk and SH2-B. APS transcripts are expressed in various tissues including brain, kidney, and muscle, as well as in splenic B cells but not in T cells. We investigated the functions of APS in B cell development and activation by generating APS-transgenic (APS-Tg) mice that overexpressed APS in lymphocytes. The number of B-1 cells in the peritoneal cavity was reduced in APS-Tg mice, as were B-2 cells in the spleen. B cell development in the bone marrow was partially impaired at the transition stage from proliferating large pre-B to small pre-B cells. B cell proliferation induced by B cell receptor (BCR) crosslinking but not by other B cell mitogens was also impaired in APS-Tg mice. APS co-localized with BCR complexes and filamentous actin in activated APS-Tg B cells. Thus, APS appears to play novel negative regulatory roles in BCR signaling, actin reorganization pathways, and control of compartment sizes of B-lineage cells. (c) 2005 Elsevier Inc. All rights reserved.