Characterization of Twixt: a novel membrane adaptor protein in B cells

描述（由申请人提供）：我们最近完成了对静息和BCR刺激的原代B细胞中酪氨酸磷酸化底物的首次全面研究。从这项工作中，我们专注于一种新的跨膜衔接蛋白，称为Twixt，由于其新奇，在B细胞中的选择性表达和潜在的重要性，在满足我们的理解BCR信号转导的知识差距-即如何BLNK是诱导招募到BCR复合物。在拟议的工作中，我们将确定Twixt是如何被BCR和其他受体招募和利用来影响下游信号传导的。这些数据将为解释Twixt缺陷小鼠中观察到的表型提供机制框架，这些表型将在第二个目标中生成和分析。完成拟议的研究将确立Twixt作为BCR信号传导中的核心参与者的重要性，或揭示更具选择性的作用。

DESCRIPTION (provided by applicant): We recently completed the first comprehensive study of tyrosine phosphorylated substrates in resting and BCR-stimulated primary B cells. From this effort, we focused on a novel transmembrane adaptor protein, termed Twixt, due to its novelty, selective expression in B cells and potential importance in fulfilling a knowledge gap in our understanding of BCR signaling - namely how BLNK is inducibly recruited to the BCR complex. In the proposed work, we will determine how Twixt is recruited and utilized by the BCR and perhaps other receptors to effect downstream signaling. These data will provide a mechanistic framework for interpreting the phenotypes observed in Twixt-deficient mice, which will be generated and analyzed in the second Aim. Completion of the proposed studies will establish the prominence of Twixt as a central player in BCR signaling, or reveal a more selective role.