Sci. STKE, 26 March 2002
Small GTPases Coincidence detector for Rac activation
The monomeric guanosine triphosphatase Rac controls major aspects of neutrophil function including chemotaxis, phagocytosis, and production of reactive oxygen species. However the guanine-nucleotide exchange factors or GEFs that regulate Rac activity are not well described. Welch et al. purified a phosphatidylinositol(3,4,5) trisphopsphate [PtdIns(3,4,5)P3]-activated Rac-GEF from pig neutrophils and then cloned the respective human gene encoding the protein they named P-Rex1. In vitro, P-Rex1 was not only directly activated by PtdIns(3,4,5)P3, but it was synergistically activated by direct interaction with G protein (heterotrimeric guanine nucleotide-binding protein) β subunits. Similar synergistic activation was observed in transfected insect SF9 cells. Such regulation of P-Rex fits nicely with its proposed role as a coincidence detector monitoring signals from Gi-coupled receptors in neutrophils, which release Gβsubunits and activate Gβ-sensitive phophoinositide-3 kinase to generate PtdIns(3,4,5)P3. The authors anticipate the P-Rex1 may also function in other cells by stimuli that cause coinicident activation of type 1A phosphoinositide 3-kinase and Gi or Go proteins.
H. C. E. Welch, W. J. Coadwell, C. D. Ellson, G. J. Ferguson, S. R. Andrews, H. Erdjument-Bromage, P. Tempst, P. T. Hawkins, L. R. Stephens, P-Rex1, a PtdIns(3,4,5)P3- and Gβ-regulated guanine-nucleotide exchange factor for Rac. Cell 108, 809-821 (2002). [Online Journal]
Citation: Coincidence detector for Rac activation. Sci. STKE 2002, tw118 (2002).
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