Phosphatidylenthanolamine Binding Protein aka Raf Kinase Inhibitor Protein: A Brief History of Its Discovery and the Remarkable Diversity of Biological Functions.
Phosphatidylenthanolamine Binding Protein aka Raf Kinase Inhibitor Protein: A Brief History of Its Discovery and the Remarkable Diversity of Biological Functions.
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DOI：
10.1615/forumimmundisther.v2.i1.20
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Sedivy JM
中科院分区：
文献类型：
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作者：
Sedivy JM
磷脂酰乙醇胺结合蛋白(PEBP)是近30年前在牛脑中发现的一种丰富的蛋白质。PEBP是一个高度保守的蛋白质家族的原型，存在于真核生物、细菌和古生菌这三个主要的系统发育类群中，与其他蛋白质没有显著的序列同源性。PEBP蛋白在许多物种中都有研究。PEBP最深入的生物学作用是细胞内信号通路的调节器，它是由其结合和抑制许多蛋白激酶的能力介导的。第一个被发现的这种相互作用是与Raf1激酶，因此PEBP在文献中被广泛地称为RKIP(Raf激酶抑制蛋白)。RKIP的活性本身受磷酸化的调节。有趣的是，PEBP还被报道具有与蛋白激酶网络无关的额外和多样化的生物学功能，这些功能仍有待详细研究。最近发现RKIP可能作为癌症转移的抑制因子，这一发现引起了人们极大的兴趣和重视。RKIP在人类癌症中的预后和治疗应用是2010年3月在加州大学洛杉矶分校举行的关于RKIP的第一次国际研讨会的主题。本文件是在研讨会上介绍的，总结了这一仍然很小但发展迅速的领域的历史。
Phosphatidylethanolamine-binding protein (PEBP) was identified almost three decades ago as an abundant protein in bovine brain. PEBP is the prototype of a highly conserved family of proteins represented in all three major phylogenetic divisions, eukaryota, bacteria, and archaea, with no significant sequence homology to other proteins. PEBP proteins have been studied in many species. The most thoroughly explored biological role of PEBP is that of a modulator of intracellular signaling pathways, which is mediated by its ability to bind and inhibit a number of protein kinases. The first such interaction that came to light was with the Raf1 kinase, and PEBP is thus widely referred to in the literature under its alternate name RKIP (Raf kinase inhibitory protein). The activity of RKIP itself is subject to regulation by phosphorylation. Intriguingly, PEBP has also been reported to possess additional, and diverse, biological functions unrelated to protein kinase networks that remain to be investigated in detail. Recent findings that RKIP may function as a suppressor of cancer metastasis are of great interest and importance. Prognostic and therapeutic applications of RKIP in human cancer were the subject of the first international workshop on RKIP that was held at the University of California, Los Angeles, in March 2010. This paper was presented at the workshop as a summary of the history of this still small but rapidly evolving field.