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

Sharon Eden, Rajat Rohatgi, Alexandre V. Podtelejnikov, Matthias Mann, Marc W. Kirschner

Research output: Contribution to journalArticlepeer-review

669 Scopus citations


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 (Mr) of 140, 000), Nap125 (NCK-associated protein with an Mr 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.

Original languageAmerican English
Pages (from-to)790-793
Number of pages4
Issue number6899
StatePublished - 15 Aug 2002
Externally publishedYes

Bibliographical note

Funding Information:
We thank H. Ho for HT–GST–WAVE1 baculovirus; B. Mayer for Nck constructs and proteins; R. Iggo for antibody to PIR121; J. Peterson and N. Ayad for discussions, technical help and critically reading the manuscript; and L. Ma for initial observations. This work was supported by the NIH (M.W.K.) the European Molecular Biology Organization (S.E.), the Human Frontier Science Program Organization (S.E.), the Danish National Research Foundation (M.M. and A.V.P.) and the Medical Sciences Training Program (MSTP) at Harvard Medical School (R.R.).


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