The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling
The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling
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DOI：
10.1016/s1534-5807(01)00009-0
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发表时间：
2001-07-01
影响因子：
11.8
通讯作者：
McClatchey, AI
中科院分区：
文献类型：
--
作者：
Shaw, RJ;Paez, JG;McClatchey, AI
神经纤维瘤病II型（NF2）肿瘤抑制基因的突变使人和小鼠易患肿瘤。对Nf2（+/-）小鼠的研究表明Nf2缺失对肿瘤转移有额外的影响。nf2编码的蛋白merlin属于ERM （ezrin， radixin和moesin）细胞骨架：膜连接物家族。然而，merlin抑制肿瘤和转移活性的分子基础尚不清楚。我们现在已经将梅林置于小GTPase Rac下游的信号通路中。活化Rac的表达可诱导磷酸化并降低merlin与细胞骨架的关联。此外，merlin过表达以磷酸化依赖的方式抑制rac诱导的信号传导。最后，Nf2（-/-）细胞表现出表达活化的Rac等位基因的细胞特征。这些研究为merlin的正常细胞功能以及Nf2突变如何促进肿瘤的发生和发展提供了见解。
Mutations in the neurofibromatosis type II (NF2) tumor suppressor predispose humans and mice to tumor development. The study of Nf2(+/-) mice has demonstrated an additional effect of Nf2 loss on tumor metastasis. The NF2-encoded protein, merlin, belongs to the ERM (ezrin, radixin, and moesin) family of cytoskeleton:membrane linkers. However, the molecular basis for the tumor- and metastasis- suppressing activity of merlin is unknown. We have now placed merlin in a signaling pathway downstream of the small GTPase Rac. Expression of activated Rac induces phosphorylation and decreased association of merlin with the cytoskeleton. Furthermore, merlin overexpression inhibits Rac-induced signaling in a phosphorylation-dependent manner. Finally, Nf2(-/-) cells exhibit characteristics of cells expressing activated alleles of Rac. These studies provide insight into the normal cellular function of merlin and how Nf2 mutation contributes to tumor initiation and progression.