Physical mechanisms of signal integration by WASP family proteins

Shae B. Padrick, Michael K. Rosen

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

The proteins of the Wiskott-Aldrich syndrome protein (WASP) family are activators of the ubiquitous actin nucleation factor, the Arp2/3 complex. WASP family proteins contain a C-terminal VCA domain that binds and activates the Arp2/3 complex in response to numerous inputs, including Rho family GTPases, phosphoinositide lipids, SH3 domain containing proteins, kinases, and phosphatases. In the archetypal members of the family, WASP and N-WASP, these signals are integrated through two levels of regulation, an allosteric autoinhibitory interaction, in which the VCA is sequestered from the Arp2/3 complex, and dimerization/oligomerization, in which multi-VCA complexes are better activators of the Arp2/3 complex than monomers. Here, we review the structural, biochemical, and biophysical details of these mechanisms and illustrate how they work together to control WASP activity in response to multiple inputs. These regulatory principles, derived from studies of WASP and N-WASP, are likely to apply broadly across the family.

Original languageEnglish (US)
Pages (from-to)707-735
Number of pages29
JournalAnnual Review of Biochemistry
Volume79
DOIs
StatePublished - Jul 7 2010

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Wiskott-Aldrich Syndrome Protein Family
Wiskott-Aldrich Syndrome Protein
Actin-Related Protein 2-3 Complex
Proteins
Allosteric Regulation
rho GTP-Binding Proteins
Oligomerization
src Homology Domains
Dimerization
Phosphoprotein Phosphatases
GTP Phosphohydrolases
Phosphatidylinositols
Protein Kinases
Actins
Nucleation
Monomers
Lipids

Keywords

  • actin regulation
  • allostery
  • Arp2/3 complex
  • Rho GTPase
  • signal transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Physical mechanisms of signal integration by WASP family proteins. / Padrick, Shae B.; Rosen, Michael K.

In: Annual Review of Biochemistry, Vol. 79, 07.07.2010, p. 707-735.

Research output: Contribution to journalArticle

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