Tyrosine phosphorylated disabled 1 recruits Crk family adapter proteins
Tyrosine phosphorylated disabled 1 recruits Crk family adapter proteins
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DOI：
10.1016/j.bbrc.2004.04.023
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发表时间：
2004-05-21
影响因子：
3.1
通讯作者：
Keshvara, L
中科院分区：
文献类型：
--
作者：
Huang, YC;Magdaleno, S;Keshvara, L
Disabled 1（Dab 1）在Reelin信号通路中作为关键的衔接蛋白发挥作用，以在脑发育期间指导神经元的适当定位。Reelin刺激Dab 1在酪氨酸198和220上的磷酸化，磷酸化的Dab 1可能与包含Src同源2（SH 2）结构域的下游信号蛋白相互作用。为了寻找这样的蛋白质，我们使用含有磷酸酪氨酸220（PTyr-220）的Dab I的琼脂糖缀合肽作为亲和基质，以捕获小鼠脑提取物中的结合蛋白。结合蛋白质的质谱分析显示，Crk家族衔接蛋白选择性地与该磷酸化位点相关。我们进一步表明，Crk-I和Crk-II，但不是CrkL，刺激磷酸化Dab 1酪氨酸220在Src依赖的方式。我们的研究结果表明，Crk家族衔接蛋白可能在大脑发育过程中的Reelin信号通路中发挥重要作用。(C)2004年爱思唯尔公司All rights reserved.
Disabled 1 (Dab 1) functions as a critical adapter protein in the Reelin signaling pathway to direct proper positioning of neurons during brain development. Reelin stimulates phosphorylation of Dab1 on tyrosines 198 and 220, and phosphorylated Dab1 is likely to interact with downstream signaling proteins that contain Src homology 2 (SH2) domains. To search for such proteins, we used a Sepharose-conjugated peptide containing phosphotyrosine 220 (PTyr-220) of Dab I, as an affinity matrix to capture binding proteins from mouse brain extracts. Mass spectrometric analysis of bound proteins revealed that Crk family adapter proteins selectively associated with this phosphorylation site. We further show that Crk-I and Crk-II, but not CrkL, stimulate phosphorylation of Dab1 on tyrosine 220 in a Src-dependent manner. Our results suggest that Crk family adapter proteins may play an important role in the Reelin signaling pathway during brain development. (C) 2004 Elsevier Inc. All rights reserved.