P‐Rex2, a new guanine‐nucleotide exchange factor for Rac

• Published in: FEBS letters 2004-08, Vol.572 (1-3), p.172-176
• Main Authors: Donald, Sarah, Hill, Kirsti, Lecureuil, Charlotte, Barnouin, Romain, Krugmann, Sonja, John Coadwell, W., Andrews, Simon R., Walker, Simon A., Hawkins, Phillip T., Stephens, Len R., Welch, Heidi C.E.
• Format: Article
• Language: English
• Subjects: Blotting, Northern; Cloning, Molecular; GEF; GEF, guanine-nucleotide exchange factor; Gene Library; Gβγ subunits; Heterotrimeric GTP-Binding Proteins - metabolism; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Organ Specificity; P-Rex1; P-Rex2; P-Rex2, phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 2; PI3K; PI3K, phosphoinositide 3-kinase; Protein Subunits - metabolism; PtdIns(3,4,5)P3, phosphatidylinositol (3,4,5)-trisphosphate; Rac; rac GTP-Binding Proteins - genetics; rac GTP-Binding Proteins - metabolism; Recombinant Proteins - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.06.096

We have identified a new guanine‐nucleotide exchange factor, P‐Rex2, and cloned it from human skeletal muscle and brain libraries. It has widespread tissue distribution but is not expressed in neutrophils. P‐Rex2 is a 183 kDa protein that activates the small GTPase Rac and is regulated by phosphatidylinositol (3,4,5)‐trisphosphate and the βγ subunits of heterotrimeric G proteins in vitro and in vivo. P‐Rex2 has structure, activity and regulatory properties similar to P‐Rex1 but has divergent tissue distribution, as P‐Rex1 is mainly expressed in neutrophils. Together, they form an enzyme family capable of mediating Rac signalling downstream of G protein‐coupled receptors and phosphoinositide 3‐kinase.