将BLNK直接招募至免疫球蛋白α可使B细胞抗原受体与远端信号通路偶联。
The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways.
作者信息
Kabak Shara, Skaggs Brian J, Gold Michael R, Affolter Michael, West Kelly L, Foster Mark S, Siemasko Karyn, Chan Andrew C, Aebersold Ruedi, Clark Marcus R
机构信息
Committee on Immunology, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA.
出版信息
Mol Cell Biol. 2002 Apr;22(8):2524-35. doi: 10.1128/MCB.22.8.2524-2535.2002.
Abstract
Following B-cell antigen receptor (BCR) ligation, the cytoplasmic domains of immunoglobulin alpha (Ig alpha) and Ig beta recruit Syk to initiate signaling cascades. The coupling of Syk to several distal substrates requires linker protein BLNK. However, the mechanism by which BLNK is recruited to the BCR is unknown. Using chimeric receptors with wild-type and mutant Ig alpha cytoplasmic tails we show that the non-immunoreceptor tyrosine-based activation motif (ITAM) tyrosines, Y176 and Y204, are required to activate BLNK-dependent pathways. Subsequent analysis demonstrated that BLNK bound directly to phospho-Y204 and that fusing BLNK to mutated Ig alpha reconstituted downstream signaling events. Moreover, ligation of the endogenous BCR induced Y204 phosphorylation and BLNK recruitment. These data demonstrate that the non-ITAM tyrosines of Ig alpha couple Syk activation to BLNK-dependent pathways.
摘要
在B细胞抗原受体（BCR）连接后，免疫球蛋白α（Igα）和Igβ的胞质结构域招募Syk以启动信号级联反应。Syk与几种远端底物的偶联需要接头蛋白BLNK。然而，BLNK被招募到BCR的机制尚不清楚。使用具有野生型和突变型Igα胞质尾巴的嵌合受体，我们发现非免疫受体酪氨酸激活基序（ITAM）酪氨酸Y176和Y204是激活BLNK依赖性途径所必需的。随后的分析表明，BLNK直接与磷酸化的Y204结合，并且将BLNK与突变的Igα融合可重建下游信号事件。此外，内源性BCR的连接诱导Y204磷酸化和BLNK招募。这些数据表明，Igα的非ITAM酪氨酸将Syk激活与BLNK依赖性途径偶联起来。
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