Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

被引：214

作者：

Serrels, Bryan ^{[1
]}

Serrels, Alan ^{[1
]}

Brunton, Valerie G. ^{[1
]}

Holt, Mark ^{[1
]}

McLean, Gordon W. ^{[1
]}

Gray, Christopher H. ^{[1
]}

Jones, Gareth E. ^{[1
]}

Frame, Margaret C. ^{[1
]}

机构：

[1] Univ Edinburgh, Queens Med Res Inst, Edinburgh EH16 4SA, Midlothian, Scotland

来源：

NATURE CELL BIOLOGY | 2007年 / 9卷 / 09期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ncb1626

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/ 3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/ 3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/ 3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/ 3, linking integrin signalling directly with the actin polymerization machinery.

引用

页码：1046 / U15

页数：18

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