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

Twixt 的表征：B 细胞中的一种新型膜接头蛋白

• 批准号: 8496712
• 负责人: ROBERT C RICKERT
• 金额: $ 22.91万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8496712
• 关键词: Adaptor Signaling Protein; Alleles; Antibody Formation; Antigens; Autoimmunity; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; BLNK gene; Binding; Biochemical; Brain region; CD19 gene; Cell Nucleus; Cell physiology; Complex; Data; Defect; Gene Expression; Genetic; Goals; Human; Immune Sera; Knowledge; Location; Measures; Membrane; Molecular; Mus; Nature; Pathway interactions; Peripheral; Phenotype; Phosphorylation; Receptor Signaling; Receptors, Antigen, B-Cell; Recruitment Activity; Rest; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Staging; Structure of germinal center of lymph node; Tyrosine; Work; base; in vivo; insight; macrophage; memory recall; novel; receptor; recombinase; research study; response; selective expression

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.

描述（由申请人提供）：我们最近完成了对静止和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，我们专注于一种新型的跨膜适配器蛋白，称为Twixt，由于其新颖性，在B细胞中的选择性表达以及在我们对BCR信号传导的理解中占据知识差距的潜在重要性 - 即BLNK如何诱导地募集到BCR复合物中。在拟议的工作中，我们将确定BCR以及其他受体如何募集和使用Twixt来实现下游信号传导。这些数据将提供一个机械框架，以解释在缺陷小鼠中观察到的表型，该表型将在第二个目标中生成和分析。拟议研究的完成将确定Twixt作为BCR信号中的核心参与者的突出性，或揭示更具选择性的作用。