The RAF family: an expanding network of post-translational controls and protein-protein interactions
The RAF family: an expanding network of post-translational controls and protein-protein interactions
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DOI：
10.1038/cr.1998.9
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发表时间：
1998-06
期刊：
影响因子：
44.1
通讯作者：
A. Yuryev;L. Wennogle
中科院分区：
文献类型：
--
作者：
A. Yuryev;L. Wennogle
蛋白激酶RAF战略性地位于“Ras-MAP-激酶信号转导途径”中，该途径是将信号从生长因子受体传递到细胞核的主要系统，导致细胞增殖。生长因子应答部分通过Ras的活化介导，Ras的活化进而活化RAF以磷酸化其下游底物MEK。MEK激活MAP激酶以影响核事件。然而，很明显，除了Ras携带的信号外，还有一个信号网络在RAF调节中发挥作用。这些正交的影响是介导的：丝氨酸/苏氨酸激酶，酪氨酸激酶，和蛋白质-蛋白质相互作用。作为RAF网络的进一步复杂化，已经建立了具有不同N-末端调节结构域的RAF的三种同种型。尽管这些不同的调控域涉及异构体特异性功能，但没有明确的证据或假说表明单个异构体具有不同的功能。最近，在与RAF相互作用的许多蛋白质中已经确定了“异构体特异性蛋白质相互作用”。这些研究可能有助于描绘RAF亚型的独立功能。
Protein kinase RAF is strategically located in the “Ras-MAP-kinase signal transduction pathway”, a principle system which transmits signals from growth factor receptors to the nucleus, resulting in cell proliferation. Growth factor responses are mediated in part by activation of Ras, which in turn activates RAF to phosphorylate MEK, its downstream substrate. MEK activates MAPkinase to influence nuclear events. It is clear, however, that a network of signals other than those carried by Ras plays a role in RAF regulation. These orthogonal influences are mediated by: serine/threonine kinases, tyrosine kinases, and protein-protein interactions. As a further complication to the RAF network, three isoforms of RAF have been established which have divergent N-terminal regulatory domains. Whereas these divergent regulatory domains implicate isoform-specific functions, no clear evidence or hypothesis for distinct functions for individual isoforms has been presented. Recently,“isoform-specific protein interactions” have been identified among numerous proteins interacting with RAF. These studies may serve to delineate independent functions for RAF isoforms.