B-CELL ANTIGEN RECEPTOR MOTIFS HAVE REDUNDANT SIGNALING CAPABILITIES AND BIND THE TYROSINE KINASES PTK72, LYN AND FYN
B-CELL ANTIGEN RECEPTOR MOTIFS HAVE REDUNDANT SIGNALING CAPABILITIES AND BIND THE TYROSINE KINASES PTK72, LYN AND FYN
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DOI：
10.1016/0960-9822(93)90062-s
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发表时间：
1993-10-01
期刊：
影响因子：
9.2
通讯作者：
DEFRANCO, AL
中科院分区：
文献类型：
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作者：
LAW, DA;CHAN, VWF;DEFRANCO, AL
背景资料：B细胞抗原受体（BCR）是一种多聚体蛋白复合物，由抗原识别结构（膜免疫球蛋白）和两种相关蛋白（Ig-α和Ig-β）组成。已经提出通过BCR的信号传导涉及Ig-α和Ig-β。这两种蛋白质在其胞质结构域内均含有存在于许多免疫识别受体（包括BCR、T细胞抗原受体和Fc受体复合物）中的氨基酸基序。这个基序，称为抗原受体同源基序（ARH 1），似乎具有信号转导能力。结果如下：我们现在表明，含有来自Ig-α或Ig-β的ARH 1基序的细胞质区域的存在足以赋予在其他方面无功能的融合蛋白的信号传导能力。含有Ig-α和Ig-β的嵌合体均以明显冗余的方式诱导膜免疫球蛋白交联后观察到的信号传导事件，包括特定蛋白质的酪氨酸磷酸化、磷酸肌醇分解和钙动员。此外，嵌合体的交联导致Ig-α和Ig-β尾的酪氨酸磷酸化及其与酪氨酸激酶PTK 72、p53/56（lym）和p59（fyn）的缔合。结论：这些观察结果表明，Ig-α和Ig-β负责将膜免疫球蛋白偶联至细胞内信号传导组分。此外，他们证明了许多酪氨酸激酶与Ig-α和Ig-β的胞质结构域直接相关。刺激嵌合体，导致Ig-α和Ig-β尾部的酪氨酸磷酸化，是这些关联中的一些的先决条件。这些研究结果的机制，BCR启动的信号反应的影响进行了讨论。
Background: The B-cell antigen receptor (BCR) is a multimeric protein complex consisting of an antigen-recognition structure (membrane immunoglobulin) and two associated proteins, Ig-alpha and Ig-beta. It has been proposed that signalling through the BCR involves Ig-alpha and Ig-beta. Both of these proteins contain within their cytoplasmic domains an amino-acid motif that is present in a number of immune recognition receptors, including the BCR, T-cell antigen receptor and Fc receptor complexes. This motif, termed the antigen-receptor homology motif (ARH1), appears to have signal transduction ability. Results: We now show that the presence of cytoplasmic regions containing the ARH1 motif from either Ig-alpha or Ig-beta is sufficient to confer signalling capability on an otherwise non-functional fusion protein. Both Ig-alpha and Ig-beta-containing chimeras induced, in an apparently redundant fashion, signalling events seen upon membrane immunoglobulin crosslinking, including tyrosine phosphorylation of particular proteins, phosphoinositide breakdown and calcium mobilization. Furthermore, crosslinking of the chimeras resulted in tyrosine phosphorylation of the Ig-alpha and Ig-beta tails and their association with the tyrosine kinases PTK72, p53/56 (lym) and p59 (fyn). Conclusions: These observations indicate that Ig-alpha and Ig-beta are responsible for coupling membrane immunoglobulin to intracellular signalling components. Moreover, they demonstrate that a number of tyrosine kinases associate directly with the cytoplasmic domains of both Ig-alpha and Ig-beta. Stimulation of the chimeras, which results in tyrosine phosphorylation of the Ig-alpha and Ig-beta tails, is a prerequisite for some of these associations. The implications of these findings for the mechanism by which the BCR initiates the signalling reactions are discussed.