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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.
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Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.

机译：鉴定一种新的跨膜衔接蛋白，该蛋白组成性结合B细胞中的Grb2。

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摘要

Transmembrane adaptor proteins couple antigen receptor engagement to downstream signaling cascades in lymphocytes. One example of these proteins is the linker for activation of T cells (LAT), which plays an indispensable role in T cell activation and development. Here, we report identification of a new transmembrane adaptor molecule, namely growth factor receptor-bound protein 2 (Grb2)-binding adaptor protein, transmembrane (GAPT), which is expressed in B cells and myeloid cells. Similar to LAT, GAPT has an extracellular domain, a transmembrane domain, and a cytoplasmic tail with multiple Grb2-binding motifs. In contrast to other transmembrane adaptor proteins, GAPT is not phosphorylated upon BCR ligation but associates with Grb2 constitutively through its proline-rich region. Targeted disruption of the gapt gene in mice affects neither B cell development nor a nitrophenylacetyl-specific antibody response. However, in the absence of GAPT, B cell proliferation after BCR cross-linking is enhanced. In aged GAPT(-/-) mice, the number of marginal zone (MZ) B cells is increased, and other B cell subsets are normal. The serum concentrations of IgM, IgG2b, and IgG3 are also elevated in these mice. These data indicate that GAPT might play an important role in control of B cell activation and proper maintenance of MZ B cells.
机译：跨膜衔接蛋白将抗原受体的结合与淋巴细胞下游的信号级联反应结合在一起。这些蛋白质的一个例子是T细胞活化（LAT）的连接子，它在T细胞活化和发育中起着不可或缺的作用。在这里，我们报告鉴定新的跨膜适配器分子，即生长因子受体结合蛋白2（Grb2）结合适配器蛋白，跨膜（GAPT），在B细胞和骨髓细胞中表达。与LAT相似，GAPT具有一个胞外域，一个跨膜域和一个带有多个Grb2结合基序的胞质尾巴。与其他跨膜衔接蛋白相反，GAPT在BCR连接后不会被磷酸化，而是通过其富含脯氨酸的区域与Grb2组成型缔合。小鼠中gapt基因的靶向破坏既不影响B细胞发育也不影响硝基苯基乙酰基特异性抗体反应。但是，在没有GAPT的情况下，BCR交联后B细胞的增殖会增强。在老年GAPT（-/-）小鼠中，边缘区（MZ）B细胞数量增加，其他B细胞亚群正常。在这些小鼠中，IgM，IgG2b和IgG3的血清浓度也升高。这些数据表明，GAPT可能在控制B细胞活化和正确维持MZ B细胞中起重要作用。

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