Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.

Abstract:

:Rac signalling to actin -- a pathway that is thought to be mediated by the protein Scar/WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin homologous protein -- has a principal role in cell motility. In an analogous pathway, direct interaction of Cdc42 with the related protein N-WASP stimulates actin polymerization. For the Rac-WAVE pathway, no such direct interaction has been identified. Here we report a mechanism by which Rac and the adapter protein Nck activate actin nucleation through WAVE1. WAVE1 exists in a heterotetrameric complex that includes orthologues of human PIR121 (p53-inducible messenger RNA with a relative molecular mass (M(r)) of 140,000), Nap125 (NCK-associated protein with an M(r) of 125,000) and HSPC300. Whereas recombinant WAVE1 is constitutively active, the WAVE1 complex is inactive. We therefore propose that Rac1 and Nck cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and leads to actin nucleation.

journal_name

Nature

journal_title

Nature

authors

Eden S,Rohatgi R,Podtelejnikov AV,Mann M,Kirschner MW

doi

10.1038/nature00859

keywords:

subject

Has Abstract

pub_date

2002-08-15 00:00:00

pages

790-3

issue

6899

eissn

0028-0836

issn

1476-4687

pii

nature00859

journal_volume

418

pub_type

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