The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling

被引：269

作者：

Shaw, RJ

Paez, JG

Curto, M

Yaktine, A

Pruitt, WM

Saotome, I

O'Bryan, JP

Gupta, V

Ratner, N

Der, CJ

Jacks, T

McClatchey, AI ^{[1
]}

机构：

[1] MGH Canc Ctr, Charlestown, MA 02129 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Ctr Canc Res, Cambridge, MA 02139 USA

[4] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[5] Harvard Med Sch, Dept Pathol, Charlestown, MA 02129 USA

[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pharmacol, Chapel Hill, NC 27599 USA

[7] Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA

来源：

DEVELOPMENTAL CELL | 2001年 / 1卷 / 01期

关键词：

D O I：

10.1016/S1534-5807(01)00009-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：63 / 72

页数：10

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