Title of article :
P-Rex1, a PtdIns(3,4,5)P3- and Gβγ-Regulated Guanine-Nucleotide Exchange Factor for Rac
Author/Authors :
Heidi C.E. Welch، نويسنده , , W.John Coadwell، نويسنده , , Christian D. Ellson، نويسنده , , John Ferguson، نويسنده , , Simon R. Andrews، نويسنده , , Hediye Erdjument-Bromage، نويسنده , , Paul Tempst، نويسنده , , Phillip T. Hawkins، نويسنده , , Len R. Stephens، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2002
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 Gβγs 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 Gβγ signaling pathways that is particularly adapted to function downstream of heterotrimeric G proteins in neutrophils.
