Raf kinase inhibitory protein (RKIP): functional pleiotropy in the mammalian brain.
Raf kinase inhibitory protein (RKIP): functional pleiotropy in the mammalian brain.
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DOI：
10.1615/critrevoncog.2014011899
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发表时间：
2014
影响因子：
--
通讯作者：
Harrod H Ling;L. Mendoza-Viveros;N. Mehta;H. M. Cheng
中科院分区：
文献类型：
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作者：
Harrod H Ling;L. Mendoza-Viveros;N. Mehta;H. M. Cheng
1984年，从牛脑中分离出一种胞浆蛋白，并将其命名为磷脂酰乙醇胺结合蛋白（PEBP），以描述其与磷脂的结合能力。它的细胞功能在十多年中一直难以捉摸，直到发现PEBP能够抑制Raf 1-丝裂原活化蛋白激酶（MAPK）通路，使其获得Raf 1激酶抑制蛋白（RKIP）的新名称。这一里程碑式的发现为许多研究铺平了道路，这些研究现在已经将RKIP的功能扩展到各种生理和病理生理系统背景下的其他信号级联。本文综述了RKIP在哺乳动物脑中的神经生理学作用，包括其在生物钟和突触可塑性中的功能。它还将讨论证据参与RKIP和其衍生的神经肽，海马胆碱能神经刺激肽（HCNP），在神经发育和分化。在某些病理学，如阿尔茨海默氏症和脑癌的影响将得到强调。通过记录RKIP在大脑中的各种功能，我们希望这篇综述将成为一个及时的资源，点燃未来对神经系统中这种多功能、多方面蛋白质的研究。
In 1984, a cytosolic protein was isolated from bovine brain and coined phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid-binding potential. Its cellular function remained elusive for more than a decade until it was discovered that PEBP had the ability to suppress the Raf1-mitogen activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase inhibitory protein (RKIP). This milestone discovery has paved the way for numerous studies that have now extended the reach of RKIP's function to other signaling cascades, within the context of various physiological and pathophysiological systems. This review will summarize our current knowledge of the neurophysiological roles of RKIP in the mammalian brain, including its function in the circadian clock and synaptic plasticity. It will also discuss evidence for an involvement of RKIP and its derived neuropeptide, hippocampal cholinergic neurostimulating peptide (HCNP), in neural development and differentiation. Implications in certain pathologies such as Alzheimer's disease and brain cancer will be highlighted. By chronicling the diverse functions of RKIP in the brain, we hope that this review will serve as a timely resource that ignites future studies on this versatile, multifaceted protein in the nervous system.