不同的人类NUMB亚型调控神经谱系中的分化与增殖。
Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.
作者信息
Verdi J M, Bashirullah A, Goldhawk D E, Kubu C J, Jamali M, Meakin S O, Lipshitz H D
机构信息
Robarts Research Institute, London, ON N6A 5K8, Canada.
出版信息
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10472-6. doi: 10.1073/pnas.96.18.10472.
Abstract
Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein-protein interaction domains: a phosphotyrosine-binding domain and a proline-rich region (PRR) that functions as an SH3-binding domain. Here we show that there are at least four human NUMB isoforms and that these serve two distinct developmental functions in the neuronal lineage: differentiation (but not proliferation) is promoted by human NUMB protein isoforms with a type I (short) PRR. In contrast, proliferation (but not differentiation) is directed by isoforms that have a type II (long) PRR. The two types of PRR may promote distinct intracellular signaling pathways downstream of the NOTCH receptor during mammalian neurogenesis.
摘要
在果蝇中，神经元细胞命运的决定由NUMB指导，NUMB是一种信号衔接蛋白，具有两个蛋白质-蛋白质相互作用结构域：一个磷酸酪氨酸结合结构域和一个富含脯氨酸的区域（PRR），该区域作为SH3结合结构域发挥作用。我们在此表明，人类至少有四种NUMB异构体，并且这些异构体在神经元谱系中发挥两种不同的发育功能：具有I型（短）PRR的人类NUMB蛋白质异构体促进分化（但不促进增殖）。相比之下，具有II型（长）PRR的异构体指导增殖（但不指导分化）。在哺乳动物神经发生过程中，这两种类型的PRR可能在NOTCH受体下游促进不同的细胞内信号通路。
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