BLNK PROTEINS IN B CELL RECEPTOR FUNCTION

B 细胞受体功能中的 BLNK 蛋白

• 批准号: 2590946
• 负责人: ANDREW C CHAN
• 金额: $ 16.91万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2590946
• 关键词: B cell receptor; B lymphocyte; binding proteins; biological signal transduction; cell differentiation; laboratory mouse; phospholipase C; phosphorylation; protein structure function

DESCRIPTION: (Adapted from the Investigator's Abstract): Stimulation of t he B-cell antigen receptor (BCR) triggers the activation of at least 3 families of protein tyrosine kinases (PTKs). The sequential activation of these PTKs orchestrates a cascade of downstream signaling events, including activation of phospholipase C (PLC), and phosphorylation of the Shc adaptor protein and the Vav protooncogene. These proteins, in turn, drive the increases in cytoplasmic free Ca2+, Ras activation, and the activation of MAP kinases that couple BCR engagement to cell-cycle entry and alterations in gene expression. The investigator has identified two novel adapter proteins, designated BLNK- 1 and BLNK-2, that bind to PLC-gamma, Grb2, and Vav. These proteins exhibit sequence and functional homologies to the slp-76 adapter protein that appears to play a central role in signal transduction through the T-cell antigen receptor (TCR). The specific aims are: (1) to characterize BLNK-1 and BLNK-2 at the molecular and biochemical levels, (2) to define the biochemical and functional interactions of BLNK-1 and BLNK-2 with PLC-gamma, Grb2 and Vav, (3) to identify the phosphorylation sites within BLNK-1, and (4) to use genetic approaches to understand the role of BLNK proteins in B-cell development and normal B-cell function.

描述：（改编自研究者摘要）：刺激 B细胞抗原受体（BCR）的激活触发了 至少3个蛋白酪氨酸激酶家族。 顺序 这些PTK的激活协调了下游信号传导的级联反应 事件，包括磷脂酶C（PLC）的激活，以及 Shc衔接蛋白和Vav原癌基因的磷酸化。 这些蛋白质反过来又驱动细胞质游离Ca2+的增加， Ras激活，以及与BCR偶联的MAP激酶的激活 参与细胞周期进入和基因表达的改变。 的 研究人员已经鉴定了两种新的衔接蛋白，命名为BLNK- 1和BLNK-2，其结合PLC-γ、Grb 2和Vav。 这些蛋白质 显示出与SLP-76衔接蛋白的序列和功能同源性 它似乎在信号转导中起着核心作用， T细胞抗原受体（TCR）。 具体目标是：（1） 在分子和生物化学水平上表征BLNK-1和BLNK-2， (2)为了确定BLNK-1的生物化学和功能相互作用， BLNK-2与PLC-γ、Grb2和Vav，（3）鉴定磷酸化 BLNK-1内的位点，以及（4）使用遗传方法来了解 BLNK蛋白在B细胞发育和正常B细胞中作用 功能