Welch Heidi C E, Coadwell W John, Ellson Christian D, Ferguson G John, Andrews Simon R, Erdjument-Bromage Hediye, Tempst Paul, Hawkins Phillip T, Stephens Len R
Inositide Laboratory, Cambridge CB2 4AT, United Kingdom.
Cell. 2002 Mar 22;108(6):809-21. doi: 10.1016/s0092-8674(02)00663-3.
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.
Rac是单体GTP酶Rho家族的成员，是多种细胞过程中细胞内信号传导的整合者。我们从中性粒细胞胞质溶胶中纯化了一种对PtdIns(3,4,5)P3敏感的Rac激活剂。它是一种丰富的185 kDa鸟嘌呤核苷酸交换因子（GEF），我们将其克隆并命名为P-Rex1。重组酶具有Rac-GEF活性，在体外和体内均受到PtdIns(3,4,5)P3和Gβγ的直接、显著且协同激活。P-Rex1反义寡核苷酸降低了中性粒细胞样细胞系中内源性P-Rex1的表达以及C5a刺激的活性氧形成。P-Rex1似乎是PtdIns(3,4,5)P3和Gβγ信号通路中的一种巧合探测器，特别适合在中性粒细胞中异源三聚体G蛋白的下游发挥作用。
