Article abstract
Nature Cell Biology 4, 574 - 582 (2002)
Published online: 15 July 2002 | doi:10.1038/ncb824
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
Enrico Brugnera1,5, Lisa Haney1,5, Cynthia Grimsley1, Mingjian Lu1, Scott F. Walk1, Annie-Carole Tosello-Trampont1, Ian G. Macara2, Hiten Madhani3, Gerald R. Fink4 & Kodimangalam S. Ravichandran1
Abstract
Mammalian Dock180 and ELMO proteins, and their homologues in Caenorhabditis elegans and Drosophila melanogaster, function as critical upstream regulators of Rac during development and cell migration. The mechanism by which Dock180 or ELMO mediates Rac activation is not understood. Here, we identify a domain within Dock180 (denoted Docker) that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro. The Docker domain is conserved among known Dock180 family members in metazoans and in a yeast protein. In cells, binding of Dock180 to Rac alone is insufficient for GTP loading, and a Dock180–ELMO1 interaction is required. We can also detect a trimeric ELMO1–Dock180–Rac1 complex and ELMO augments the interaction between Dock180 and Rac. We propose that the Dock180–ELMO complex functions as an unconventional two-part exchange factor for Rac.
- Beirne Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
- Department of Pharmacology and the Markey Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA
- Department of Biochemistry and Biophysics, University of California-San Francisco, San Francisco, CA 94143, USA
- Whitehead Institute, Nine Cambridge Center, Cambridge MA 02142, USA
- These authors contributed equally to this work
Correspondence to: Kodimangalam S. Ravichandran1 e-mail: Ravi@virginia.edu
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