TY - JOUR
T1 - Physical mechanisms of signal integration by WASP family proteins
AU - Padrick, Shae B.
AU - Rosen, Michael K.
PY - 2010/7/7
Y1 - 2010/7/7
N2 - 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.
AB - 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.
KW - Arp2/3 complex
KW - Rho GTPase
KW - actin regulation
KW - allostery
KW - signal transduction
UR - http://www.scopus.com/inward/record.url?scp=77953637330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953637330&partnerID=8YFLogxK
U2 - 10.1146/annurev.biochem.77.060407.135452
DO - 10.1146/annurev.biochem.77.060407.135452
M3 - Review article
C2 - 20533885
AN - SCOPUS:77953637330
SN - 0066-4154
VL - 79
SP - 707
EP - 735
JO - Annual review of biochemistry
JF - Annual review of biochemistry
ER -