The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
The function of rac, a ras-related GTP-binding protein, was investigated in fibroblasts by microinjection. In confluent serum-starved Swiss 3T3 cells, rac1 rapidly stimulated actin filament accumulation at the plasma membrane, forming membrane ruffles. Several growth factors and activated H-ras also induced membrane ruffling, and this response was prevented by a dominant inhibitory mutant rac protein, N17rac1. This suggests that endogenous rac proteins are required for growth factor-induced membrane ruffling. In addition to membrane ruffling, a later response to both rac1 microinjection and some growth factors was the formation of actin stress fibers, a process requiring endogenous rho proteins. Using N17rac1 we have shown that these growth factors act through rac to stimulate this rho-dependent response. We propose that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin.
Ridley
A J
AJ
Institute for Cancer Research, Chester Beatty Laboratories, London, England.
Paterson
H F
HF
Johnston
C L
CL
Diekmann
D
D
Hall
A
A
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D016895:Culture Media, Serum-Free; D003599:Cytoskeleton / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors / Q000502:physiology; D010873:Pinocytosis; D013379:Substrate Specificity; D020744:rac GTP-Binding Proteins
D000199:Actins; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); D020744:rac GTP-Binding Proteins