BLNK PROTEINS IN B CELL RECEPTOR FUNCTION

描述：(改编自《调查者摘要》)：刺激 B细胞抗原受体(BCR)激活AT 蛋白酪氨酸激酶(PTK)家族至少有3个。顺序号 这些PTK的激活协调了下游信号的级联 事件，包括磷脂酶C(PLC)的激活，以及 Shc接头蛋白和Vav原癌基因的磷酸化。 这些蛋白质反过来推动细胞质内游离钙离子的增加， 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。这个 研究人员发现了两种新的接头蛋白，命名为BLNK- 1和BLNK-2，与PLC-γ、Grb2和Vav结合。这些蛋白质 展示与SLP-76接头蛋白的序列和功能同源性 这似乎在信号转导中发挥着核心作用，通过 T细胞抗原受体(TCR)。具体目标是：(1) 从分子和生化水平鉴定BLNK-1和BLNK-2， (2)明确BLNK-1与BLNK-1的生化和功能相互作用 BLNK-2与PLC-γ、Grb2和Vav结合，(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细胞中的作用 功能。

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.