Lnk and Lnk-family adaptor proteins in lymphocyte development.

Lnk在T细胞和B细胞中表达，可能与Grb 2、PLCγ和PI 3 K相互作用，是一种参与淋巴细胞信号转导的接头蛋白。缺乏Lnk表达的动物没有表现出任何明显的发育异常，并且在大小、活动和生育力方面是正常的。尽管胸腺中的T细胞发育不受影响，但前B细胞和未成熟的B细胞在Lnk-/-小鼠的脾脏中积累。在骨髓中，观察到前B细胞部分显著扩增，导致更成熟B细胞前体的代表性成比例增加。这种B细胞前体的增加是由增殖增强引起的，这是由于B细胞前体内的内在缺陷，如骨髓转移实验所证明的。在Lnk-/-未成熟骨髓细胞中，c-Kit介导的增殖反应增强。我们的研究结果表明，一个特定的，细胞自主功能的LNK限制B淋巴细胞生成。对Lnk-/-小鼠的进一步表征还显示，全长Lnk蛋白的大小几乎是先前公开的蛋白的两倍。全长Lnk含有富含脯氨酸的区域，随后是PH结构域、SH 2结构域和保守基序，该保守基序包含候选酪氨酸磷酸化位点。Lnk是一个多基因家族的代表，其成员可能是酪氨酸激酶介导的信号负调节因子，我们试图鉴定另一个衔接蛋白家族成员并分离小鼠APS，APS在脑、肾、肌肉和脾的B细胞中表达。APS通过B细胞sIgM的交联在C-末端磷酸化位点被酪氨酸磷酸化。APS可能在B细胞的信号传导中起作用。

Lnk is an adaptor protein that appears to be involved in signal transduction in lymphocytes, based on its expression in T cells and B cells and possible interaction with Grb2, PLCγ and PI3K.To illuminate the importance of Lnk in signal transduction, we generated Lnk-deficient mice. Animals lacking Lnk expression did not show any overt developmental abnormalities and were normal in size, activity, and fertility. Whereas T-cell development in the thymus was not affected, pre-B cells and immature B cells accumulated in the spleens of Lnk-/-mice. In the bone marrow, a significant expansion of the pro-B cell fraction leading to a proportionate increase in the representation of more mature B-cell precursors was observed. This increase in B-cell precursors resulted from enhanced proliferation, due to intrinsic defects within B cell precursors as demonstrated by bone marrow transfer experiments. Proliferative responses mediated by c-Kit were augmented in the Lnk-/-immature bone marrow cells. Our results suggest a specific, cell-autonomous function of Lnk in limiting B-lymphopoiesis. Further characterization of Lnk-/-mice also revealed that the full length Lnk protein is nearly twice the size of the previously published protein. Full length Lnk contains a proline-rich region followed by a PH domain, an SH2 domain, and a conserved motif harboring a candidate tyrosine phosphorylation site. Lnk is a representative of a multigene family whose members presumably function as a negative regulator of signaling mediated by tyrosine kinases.We tried to identify another member of the adaptor protein family and isolated the mouse APS.APS is expressed in brain, kidney, muscle, and in B cells in spleen. APS is tyrosine phosphorylated at the C-terminal phosphorylation site by crosslinking of sIgM of B cells. APS is likely to play a role in signaling in B cells.