SOCS36E 与 Drk 之间的竞争调节 Sevenless 受体酪氨酸激酶活性。
Competition between SOCS36E and Drk modulates Sevenless receptor tyrosine kinase activity.
机构信息
Departament de Genètica, Facultat de Biologia and Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
出版信息
J Cell Sci. 2010 Nov 15;123(Pt 22):3857-62. doi: 10.1242/jcs.071134. Epub 2010 Oct 27.
Modulation of signalling pathways can trigger different cellular responses, including differences in cell fate. This modulation can be achieved by controlling the pathway activity with great precision to ensure robustness and reproducibility of the specification of cell fate. The development of the photoreceptor R7 in the Drosophila melanogaster retina has become a model in which to investigate the control of cell signalling. During R7 specification, a burst of Ras small GTPase (Ras) and mitogen-activated protein kinase (MAPK) controlled by Sevenless receptor tyrosine kinase (Sev) is required. Several cells in each ommatidium express sev. However, the spatiotemporal expression of the boss ligand and the action of negative regulators of the Sev pathway will restrict the R7 fate to a single cell. The Drosophila suppressor of cytokine signalling 36E (SOCS36E) protein contains an SH2 domain and acts as a Sev signalling attenuator. By contrast, downstream of receptor kinase (Drk), the fly homolog of the mammalian Grb2 adaptor protein, which also contains an SH2 domain, acts as a positive activator of the pathway. Here, we apply the Förster resonance energy transfer (FRET) assay to transfected Drosophila S2 cells and demonstrate that Sev binds directly to either the suppressor protein SOCS36E or the adaptor protein Drk. We propose a mechanistic model in which the competition between these two proteins for binding to the same docking site results in either attenuation of the Sev transduction in cells that should not develop R7 photoreceptors or amplification of the Ras-MAPK signal only in the R7 precursor.
信号通路的调节可以触发不同的细胞反应,包括细胞命运的差异。这种调节可以通过精确控制途径活性来实现,以确保细胞命运特化的稳健性和可重复性。果蝇视网膜中的光感受器 R7 的发育已成为研究细胞信号控制的模型。在 R7 特化过程中,需要 Sev 受体酪氨酸激酶(Sev)控制的 Ras 小 GTPase(Ras)和丝裂原活化蛋白激酶(MAPK)的爆发。每个小眼的几个细胞都表达 sev。然而,boss 配体的时空表达和 Sev 途径的负调节因子的作用将限制 R7 命运到单个细胞。果蝇细胞因子信号转导抑制物 36E(SOCS36E)蛋白含有一个 SH2 结构域,作为 Sev 信号的衰减子。相比之下,在受体激酶(Drk)下游,果蝇与哺乳动物 Grb2 衔接蛋白的同源物,也含有一个 SH2 结构域,作为途径的正激活物。在这里,我们应用Förster 共振能量转移(FRET)测定法转染的果蝇 S2 细胞,并证明 Sev 直接结合到抑制蛋白 SOCS36E 或衔接蛋白 Drk。我们提出了一个机制模型,其中这两种蛋白竞争与同一停靠位点结合,导致不应该发育 R7 光感受器的细胞中的 Sev 转导衰减,或者仅在 R7 前体中放大 Ras-MAPK 信号。