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The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling

Nature Cell Biology volume 4, pages 970–975 (2002)Cite this article

Abstract

WAVE-1, which is also known as Scar, is a scaffolding protein that directs actin reorganization by relaying signals from the GTPase Rac to the Arp2/3 complex. Although the molecular details of WAVE activation by Rac have been described, the mechanisms by which these signals are terminated remain unknown. Here we have used tandem mass spectrometry to identify previously unknown components of the WAVE signalling network including WRP, a Rac-selective GTPase-activating protein. WRP binds directly to WAVE-1 through its Src homology domain 3 and specifically inhibits Rac function in vivo. Thus, we propose that WRP is a binding partner of WAVE-1 that functions as a signal termination factor for Rac.

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Figure 1: The WAVE-1 protein network and characterization of WRP.
Figure 2: Defining the interactive surfaces on WRP and WAVE-1.
Figure 3: WRP is a Rac-selective GTPase-activating protein.

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Acknowledgements

We thank L. Langeberg for help preparing the manuscript; R. Mouton for technical assistance; C. S. Boone and M. Evangelista for sharing unpublished data and for critical review of the manuscript; and T. R. Soderling for support. This work was supported by grants from the National Institutes of Health, the Canadian Institutes of Health Research (CIHR), the National Cancer Institute of Canada (NCIC) and the Ontario R&D Challenge Fund (J.D.S., T.P. & G.A.W.). T.P. is a CIHR Distinguished Scientist. K.L.B. is supported by a National Science and Engineering Research Council of Canada (NSERC)/MDS-Sciex Industrial Postgraduate Scholarship. S.H.O. is supported by a postdoctoral fellowship from the National Medical Research Council of Singapore.

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Author notes

  1. Scott H. Soderling and Kathleen L. Binns: These authors contributed equally to this work

Authors and Affiliations

  1. Howard Hughes Medical Institute, Vollum Institute, 3181 Sam Jackson Park Road, Portland, 97239-3098, Oregon, USA

    Scott H. Soderling, Stephen M. Davee & John D. Scott

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Ontario, Canada

    Kathleen L. Binns & Siew Hwa Ong

  3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, M5G 1X5, Ontario, Canada

    Kathleen L. Binns & Tony Pawson

  4. Vollum Institute, 3181 Sam Jackson Park Road, Portland, 97239-3098, Oregon, USA

    Gary A. Wayman

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  1. Scott H. Soderling
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Correspondence to John D. Scott.

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Supplementary information

Supplementary figures and methods

Figure S1. Immunocytochemical experiments were performed to confirm the mass spectrometry and biochemical data and assess the cellular distribution of WRP and WAVE. (PDF 300 kb)

Figure S2. HEK293 cells were transfected with WRP or WRPGAP and Rac-GTP levels were measured by the Pak-1 capture assay.

Supplementary Methods

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Soderling, S., Binns, K., Wayman, G. et al. The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. Nat Cell Biol 4, 970–975 (2002). https://doi.org/10.1038/ncb886

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