Hierarchical Regulation of WASP/WAVE Proteins

被引：161

作者：

Padrick, Shae B. ^{[1
,2
]}

Cheng, Hui-Chun ^{[1
,2
]}

Ismail, Ayman M. ^{[1
,2
]}

Panchal, Sanjay C. ^{[1
,2
]}

Doolittle, Lynda K. ^{[1
,2
]}

Kim, Soyeon ^{[1
,2
]}

Skehan, Brian M. ^{[3
]}

Umetani, Junko ^{[1
,2
]}

Brautigam, Chad A. ^{[2
]}

Leong, John M. ^{[3
]}

Rosen, Michael K. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[3] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA

来源：

MOLECULAR CELL | 2008年 / 32卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.molcel.2008.10.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.

引用

页码：426 / 438

页数：13

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