Rac GTPase interacts specifically with phosphatidylinositol 3-kinase.
The Rac GTP-binding proteins are members of the Rho family and regulate growth factor-stimulated actin assembly in a variety of cells. The formation of phosphorylated inositol lipids has been implicated in control of the processes initiating and regulating such actin polymerization. Associations of Rho family GTP-binding proteins with enzymes involved in lipid metabolism have been described. Here we demonstrate a direct and specific interaction of Rac proteins with phosphatidylinositol (PI) 3-kinase. This interaction is dependent upon Rac being in a GTP-bound state and requires an intact Rac effector domain. In contrast, direct binding of RhoA to PI 3-kinase could not be detected. Rac-GTP also bound to PI 3-kinase in Swiss 3T3 fibroblast and human neutrophil lysates, and increased PI 3-kinase activity became associated with Rac-GTP in platelet-derived growth factor-stimulated cells. Interaction of Rac-GTP with PI 3-kinase in vitro stimulated the activity of the enzyme by 2-9-fold. A specific interaction of active Rac with PI 3-kinase might be important in regulation of the actin cytoskeleton.
Bokoch
G M
GM
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Vlahos
C J
CJ
Wang
Y
Y
Knaus
U G
UG
Traynor-Kaplan
A E
AE
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003599:Cytoskeleton / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
D000199:Actins; D006160:Guanosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein