CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP
CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP
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DOI：
10.1074/jbc.m605693200
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发表时间：
2006-09-29
影响因子：
4.8
通讯作者：
Taniguchi, Hisaaki
中科院分区：
文献类型：
--
作者：
Konishi, Hiroaki;Tashiro, Kyoko;Taniguchi, Hisaaki
为了破译表皮生长因子(EGF)受体介导的信号通路的全球网络，对酪氨酸磷酸化蛋白进行了大规模的蛋白质组学分析。在这里，我们重点研究了一种新的蛋白质，CFBP(CIN85/CD2AP家族结合蛋白)，它是在研究中发现的。在EGF刺激下，CFBP被发现在酪氨酸204处被磷酸化，CIN85/CD2AP家族被确定为结合伙伴。CIN85/CD2AP的3个Src同源结构域中的一个识别CFBP富含Pro的基序，相互作用的亲和力由CFBP的酪氨酸磷酸化调节。它们共定位在富含放线蛋白的结构中，CFBP的过表达导致了肌动蛋白重组的形态变化。此外，CFBP通过促进Cb1重新募集到CD2AP/CIN85复合体，加速了EGF受体的下调。CFBP的两个缺失外显子5或8的剪接变体也被表达，而缺失外显子5而没有富含Pro基序的变体缺乏与CIN85/CD2AP家族结合的能力。CFBP蛋白似乎在配体介导的EGF受体内化和下调中起关键作用。
To decipher the global network of the epidermal growth factor (EGF) receptor-mediated signaling pathway, a large scale proteomic analysis of tyrosine-phosphorylated proteins was conducted. Here, we focus on characterizing a novel protein, CFBP (CIN85/CD2AP family binding protein), identified in the study. CFBP was found to be phosphorylated at tyrosine 204 upon EGF stimulation, and the CIN85/CD2AP family was identified as a binding partner. A proline-rich motif of CFBP is recognized by one of the three Src-homology 3 domains of CIN85/CD2AP, and the affinity of the interaction is regulated by the tyrosine phosphorylation of CFBP. They co-localize in actinen-riched structures, and overexpression of CFBP induced morphological changes with actin reorganization. Furthermore, CFBP accelerated the EGF receptor's down-regulation by facilitating the recruitment of Cbl to the CD2AP/CIN85 complex. Two spliced variants of CFBP lacking either exon 5 or 8 are also expressed, and the variant lacking exon 5 without the proline-rich motif lacks the ability to bind to the CIN85/CD2AP family. The CFBP protein seems to play a key role in the ligand-mediated internalization and down-regulation of the EGF receptor.