Grb2, a double-edged sword of receptor tyrosine kinase signaling.
Grb2, a double-edged sword of receptor tyrosine kinase signaling.
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DOI：
10.1126/scisignal.2003576
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发表时间：
2012-11-06
影响因子：
7.3
通讯作者：
Mohammadi M
中科院分区：
文献类型：
--
作者：
Belov AA;Mohammadi M
受体酪氨酸激酶（RTK）在没有配体刺激的情况下表现出基础酪氨酸磷酸化和活性，这归因于酪氨酸激酶自抑制的“泄漏”性质和膜双层中受体的随机碰撞。这种基础磷酸化不产生足够幅度和强度的信号以在生物反应中表现出来，因此被认为是一种被动的、无效的过程，不具有任何生物功能。这种模式现在已经受到挑战的研究表明，RTK的基础磷酸化是一个生理相关的过程，积极抑制细胞内衔接蛋白生长因子受体结合2（Grb 2），并用于“总理”受体的快速响应配体刺激。Grb2通常被认为在RTK信号中发挥积极作用。Grb2负调控作用的发现表明，这种适配器在RTK信号的调节中充当双刃剑。
Receptor tyrosine kinases (RTKs) exhibit basal tyrosine phosphorylation and activity in the absence of ligand stimulation, which has been attributed to the “leaky” nature of tyrosine kinase autoinhibition and stochastic collisions of receptors in the membrane bilayer. This basal phosphorylation does not produce a signal of sufficient amplitude and intensity to manifest in a biological response and hence is considered to be a passive, futile process that does not have any biological function. This paradigm has now been challenged by a study showing that the basal phosphorylation of RTKs is a physiologically relevant process that is actively inhibited by the intracellular adaptor protein growth factor receptor-bound 2 (Grb2) and serves to “prime” receptors for a rapid response to ligand stimulation. Grb2 is conventionally known for playing positive roles in RTK signaling. The discovery of a negative regulatory role for Grb2 reveals that this adaptor acts as a double-edged sword in the regulation of RTK signaling.
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