Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage
Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage
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DOI：
10.1073/pnas.96.18.10472
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发表时间：
1999-08-31
影响因子：
11.1
通讯作者：
Lipshitz, HD
中科院分区：
文献类型：
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作者：
Verdi, JM;Bashirullah, A;Lipshitz, HD
果蝇神经细胞命运的决定是导演的麻木,信号适配器蛋白质有两个域:蛋白质间交互作用phosphotyrosine-binding域和脯氨酸区域(PRR)函数作为SH3-binding域,我们表明,至少有四人麻木亚型和这些服务两个截然不同的神经发育功能血统:分化(但不是扩散)是由人类麻木蛋白质与I型(短)PRR亚型。相比之下，增殖（而不是分化）是由具有II型（长）PRR的亚型指导的。在哺乳动物神经发生过程中，这两种类型的PRR可能促进NOTCH受体下游不同的细胞内信号通路。
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.