| Literature DB >> 11955434 |
Heidi C E Welch1, W John Coadwell, Christian D Ellson, G John Ferguson, Simon R Andrews, Hediye Erdjument-Bromage, Paul Tempst, Phillip T Hawkins, Len R Stephens.
Abstract
Rac, a member of the Rho family of monomeric GTPases, is an integrator of intracellular signaling in a wide range of cellular processes. We have purified a PtdIns(3,4,5)P3-sensitive activator of Rac from neutrophil cytosol. It is an abundant, 185 kDa guanine-nucleotide exchange factor (GEF), which we cloned and named P-Rex1. The recombinant enzyme has Rac-GEF activity that is directly, substantially, and synergistically activated by PtdIns(3,4,5)P3 and Gbetagammas both in vitro and in vivo. P-Rex1 antisense oligonucleotides reduced endogenous P-Rex1 expression and C5a-stimulated reactive oxygen species formation in a neutrophil-like cell line. P-Rex1 appears to be a coincidence detector in PtdIns(3,4,5)P3 and Gbetagamma signaling pathways that is particularly adapted to function downstream of heterotrimeric G proteins in neutrophils.Entities:
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Year: 2002 PMID： 11955434 DOI： 10.1016/s0092-8674(02)00663-3
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582