P-Rex1, a PtdIns(3,4,5)P3- and gβγ-regulated guanine-nucleotide exchange factor for Rac Journal Article
| Authors: | Welch, H. C. E.; Coadwell, W. John; Ellson, C. D.; Ferguson, G. John; Andrews, S. R.; Erdjument-Bromage, H.; Tempst, P.; Hawkins, P. T.; Stephens, L. R. |
| Article Title: | P-Rex1, a PtdIns(3,4,5)P3- and gβγ-regulated guanine-nucleotide exchange factor for Rac |
| 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. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; nonhuman; protein function; animal cell; phenotype; animals; cell line; protein; enzyme activity; recombinant enzyme; animalia; cloning, molecular; regulatory mechanism; amino acid sequence; molecular sequence data; neutrophil; protein purification; platelet-derived growth factor; reactive oxygen species; reactive oxygen metabolite; cell fractionation; neutrophils; protein family; phosphoric monoester hydrolases; swine; cytosol; rac protein; heterotrimeric guanine nucleotide binding protein; guanine nucleotide exchange factors; rho factor; guanine nucleotide exchange factor; guanosine triphosphatase; rac gtp-binding proteins; antisense oligonucleotide; heterotrimeric gtp-binding proteins; humans; human; priority journal; article; phosphatidylinositol phosphates; complement component c5a; protein p rex1 |
| Journal Title: | Cell |
| Volume: | 108 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2002-03-01 |
| Start Page: | 809 |
| End Page: | 821 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(02)00663-3 |
| PUBMED: | 11955434 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
