Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion

被引：134

作者：

Kitzing, Thomas M.

Sahadevan, Arul S.

Brandt, Dominique T.

Knieling, Helga

Hannemann, Sebastian

Fackler, Oliver T.

GroBhans, Joerg

Grosse, Robert

机构：

[1] Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany

[2] Univ Heidelberg, Dept Virol, D-69120 Heidelberg, Germany

[3] Univ Heidelberg, Zentrum Mol Biol Heidelberg, D-69120 Heidelberg, Germany

来源：

GENES & DEVELOPMENT | 2007年 / 21卷 / 12期

关键词：

diaphanous-related formins; RhoA; LARG; actin polymerization; LPA; Rho-kinase;

D O I：

10.1101/gad.424807

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The RhoA-effector Dia1 controls actin-dependent processes such as cytokinesis, SRF transcriptional activity, and cell motility. Dia1 polymerizes actin through its formin homology (FH) 2 domain. Here we show that Dia1 acts upstream of RhoA independently of its effects on actin assembly. Dia1 binds to the leukemia-associated Rho-GEF (LARG) through RhoA-dependent release of Dia1 autoinhibition. The FH2 domain stimulates the guanine nucleotide exchange activity of LARG in vitro. Our results reveal that Dia1 is necessary for LPA-stimulated Rho/ROCK signaling and bleb-associated cancer cell invasion. Thus, Dia1-dependent RhoA activation constitutes a positive feedback mechanism to modulate cell behavior.

引用

页码：1478 / 1483

页数：6

共 32 条

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