Caenorhabditis elegans genes sma2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components

Caenorhabditis elegans genes sma2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components
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DOI:
10.1073/pnas.93.2.790
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发表时间:
1996-01-23
影响因子:
11.1
通讯作者:
Padgett, RW
Padgett, RW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Savage, C;Das, P;Padgett, RW

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虽然转化生长因子β (tgf - β)超家族配体在多种发育过程中发挥着关键作用,但细胞如何转导这些配体的信号仍然知之甚少,这些配体的细胞表面受体已经确定,但它们的细胞质靶点尚不清楚。我们已经确定了三个秀丽隐杆线虫基因,sma-2, sma-3和sma-4,它们具有与tgf - β样受体基因daf-4相似的突变表型。我们发现sma-2与daf-4在相同的细胞中起作用,与受体转导信号的作用一致,这三个基因定义了一个蛋白质家族,侏儒,其中包括Mad基因产物,它参与果蝇的decapentapental瘫tgf - β样途径[Sekelsky, J. J., Newfeld, S. J., Raftery, L. a ., Chartoff, E. H. & Gelbart, W. M.(1995)遗传学139,1347-1358]。这些通路的同源成分在远亲生物中的鉴定表明,矮子可能是tgf - β样信号转导的普遍需要。事实上,我们已经从脊椎动物中分离出高度保守的矮子,表明这些成分不是无脊椎动物所特有的。这些分析表明,矮子是保守的细胞质信号转导。
Although transforming growth factor beta (TGF-beta) superfamily ligands play critical roles in diverse developmental processes, how cells transduce signals from these ligands is still poorly understood, Cell surface receptors for these ligands have been identified, but their cytoplasmic targets are unknown, We have identified three Caenorhabditis elegans genes, sma-2, sma-3, and sma-4, that have mutant phenotypes similar to those of the TGF-beta-like receptor gene daf-4, indicating that they are required for daf-4-mediated developmental processes, We show that sma-2 functions in the same cells as daf-4, consistent with a role in transducing signals from the receptor, These three genes define a protein family, the dwarfins, that includes the Mad gene product, which participates in the decapentaplegic TGF-beta-like pathway in Drosophila [Sekelsky, J. J., Newfeld, S. J., Raftery, L. A., Chartoff, E. H. & Gelbart, W. M. (1995) Genetics 139, 1347-1358], The identification of homologous components of these pathways in distantly related organisms suggests that dwarfins may be universally required for TGF-beta-like signal transduction, In fact, we have isolated highly conserved dwarfins from vertebrates, indicating that these components are not idiosyncratic to invertebrates, These analyses suggest that dwarfins are conserved cytoplasmic signal transducers.