Differential activation of the Rac pathway by Ha-Ras and K-Ras.
Ras proteins are key regulators of cell growth and differentiation. Mammalian cells express three closely related Ras proteins: Ha-Ras, K-Ras, and N-Ras. We have compared the abilities of the Ha-Ras and K-Ras isoforms to activate the Rac effector pathway, using three Rac-dependent readouts: induction of membrane ruffling and pinocytosis, stimulation of cell motility, and Pak binding. The total surface area of membrane ruffles induced by K-RasV12 was 2-fold greater than that induced by Ha-RasV12. Likewise, the number of K-RasV12-induced pinocytic vesicles per cell was approximately 2-fold greater than that induced by Ha-RasV12. In a wound healing assay, K-RasV12-injected cells migrated twice as fast as Ha-RasV12-injected cells. Moreover, the Pak binding activity of Rac, which is indicative of the amount of GTP-bound Rac, was higher in K-RasV12-expressing cells than Ha-RasV12-expressing cells. These results suggest that K-Ras activates Rac more efficiently than Ha-Ras. The preferential activation of Rac by K-Ras is dependent on the mode of membrane anchoring and impacts on the ability of K-Ras to regulate cell survival.
Walsh
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AB
Department of Molecular Genetics and Microbiology and the Graduate Program in Physiology and Biophysics, State University of New York, Stony Brook, New York 11794, USA.
Bar-Sagi
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D
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure*; D002522:Chlorocebus aethiops; D006801:Humans; D008322:Mammals; D010873:Pinocytosis; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D011994:Recombinant Proteins; D020744:rac GTP-Binding Proteins; D018631:ras Proteins