The serine and threonine residues in the Ig-α cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signal transduction
The serine and threonine residues in the Ig-α cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signal transduction
复制标题
DOI：
10.1073/pnas.97.15.8451
复制
发表时间：
2000-07-18
影响因子：
11.1
通讯作者：
Reth, M
中科院分区：
文献类型：
--
作者：
Müller, R;Wienands, J;Reth, M
B 细胞抗原受体 (BCR) 是一种多蛋白复合物，由膜结合 Ig 分子和 Ig-α/Ig-β 异二聚体组成。在 BCR 参与时，Ig-α 和 Ig-β 不仅在基于酪氨酸的免疫受体激活基序的酪氨酸残基上磷酸化，而且还在丝氨酸和苏氨酸残基上磷酸化。我们已将 Ig-α 尾部的所有丝氨酸和苏氨酸残基突变为丙氨酸和缬氨酸。分别。突变的 Ig-α 序列表达为单链 Fv/Ig-α 分子或在完整 BCR 的背景下表达。在这两种情况下，突变的 Ig-α 均表现出比野生型 Ig-α 更强的酪氨酸磷酸化，并在刺激时引发信号传导增强。这些发现表明丝氨酸/苏氨酸激酶可以负向调节 BCR 的信号转导。
The B cell antigen receptor (BCR) is a multiprotein complex consisting of the membrane-bound Ig molecule and the Ig-alpha/Ig-beta heterodimer. On BCR engagement, Ig-alpha and Ig-beta become phosphorylated not only on tyrosine residues of the immunoreceptor tyrosine-based activation motif but also on serine and threonine residues. We have mutated all serine and threonine residues in the Ig-alpha tail to alanine and valine. respectively. The mutated Ig-alpha sequence was expressed either as a single-chain Fv/Ig-alpha molecule or in the context of the complete BCR. In both cases, the mutated Ig-alpha showed a stronger tyrosine phosphorylation than the wild type Ig-alpha and initiated increased signaling on stimulation. These findings suggest that serine/threonine kinases can negatively regulate signal transduction from the BCR.