C-elegans cell migration gene mig-10 shares similarities with a family of SH2 domain proteins and acts cell nonautonomously in excretory canal development

C-elegans cell migration gene mig-10 shares similarities with a family of SH2 domain proteins and acts cell nonautonomously in excretory canal development
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DOI:
10.1006/dbio.1997.8516
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发表时间:
1997-04-01
影响因子:
2.7
通讯作者:
Margolis, B
Margolis, B
中科院分区:
生物学3区
文献类型:
--
作者:
Manser, J;Roonprapunt, C;Margolis, B

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秀丽隐杆线虫的mig-10基因是胚胎神经元CAN、ALM和HSN的长距离前后迁移和排泄管的正常发育所必需的。在这里,我们报告的mig-10的克隆和初步的分子特征。所预测的GRB 10蛋白与最近鉴定的哺乳动物SH 2结构域蛋白家族Grb 7和Grb 10具有很大的相似性。我们称这个相似区域为GM区域(对于Grb和Mig)。β-10蛋白不含SH 2结构域,但与Grbs共享普列克底物蛋白同源(PII)结构域和富含脯氨酸的区域,这些特征通常在信号转导蛋白中发现。Grb 7和Grb 10的功能尚不清楚,但Grb 7在某些乳腺癌中过表达,它与生长因子受体HER 2结合,而Grb 10与胰岛素信号传导有关。我们还报告了一个新的mig-10(e2527)等位基因的分离,以及e2527(剪接受体突变)和典型的ct 41(琥珀)等位基因的分子特征。最后,我们报告了一个遗传嵌合体分析的结果,该分析揭示了mig-10在排泄管的发育中非自主地作用于细胞,并提出了mig-10在AB细胞谱系的后代中的活性的可能焦点。mig-10在C. elegans的发展将导致更好地理解细胞迁移,并可能揭示一个家族的SH 2结构域蛋白的功能,显然参与信号转导和癌症。(C)北京:科学出版社.
The mig-10 gene of Caenorhabditis elegans is required for the long-range anteroposterior migration of embryonic neurons CAN, ALM, and HSN and proper development of the excretory canals. Here, we report the cloning and initial molecular characterization of mig-10. The predicted MIG-10 proteins share a large region of similarity with a recently identified family of mammalian SH2 domain proteins, Grb7 and Grb10. We call this region of similarity the GM region (for Grb and Mig). MIG-10 proteins do not contain an SH2 domain, but share with the Grbs a pleckstrin homology (PII) domain and proline-rich regions, features commonly found in signal transduction proteins. The functions of Grb7 and Grb10 are unknown, but Grb7 is overexpressed in certain breast cancers, where it is bound to the growth factor receptor HER2, while Grb10 has been implicated in insulin signaling. We also report the isolation of a new mig-10(e2527) allele, as well as the molecular characterization of e2527 (splice acceptor mutation) and the canonical ct41 (amber) allele. finally, we report the results of a genetic mosaic analysis which reveal that mig-10 acts cell nonautonomously in the development of the excretory canals and suggest a possible focus for mig-10 activity within descendants of the AB cell lineage. Elucidation of the role of mig-10 in C. elegans development should lead to a better understanding of cell migration and may shed light on the function of a family of SH2 domain proteins apparently involved in signal transduction and cancer. (C) 1997 Academic Press.