Abstract
In COS cells, Ral GDP dissociation stimulator (RalGDS)-induced Ral activation was stimulated by RasG12V or a Rap1/Ras chimera in which the N-terminal region of Rap1 was ligated to the C-terminal region of Ras but not by Rap1G12V or a Ras/Rap1 chimera in which the N-terminal region of Ras was ligated to the C-terminal region of Rap1, although RalGDS interacted with these small GTP-binding proteins. When RasG12V, Ral and the Rap1/Ras chimera were individually expressed in NIH3T3 cells, they localized to the plasma membrane. Rap1Q63E and the Ras/Rap1 chimera were detected in the perinuclear region. When RalGDS was expressed alone, it was abundant in the cytoplasm. When coexpressed with RasG12V or the Rap1/Ras chimera, RalGDS was detected at the plasma membrane, whereas when coexpressed with Rap1Q63E or the Ras/Rap1 chimera, RalGDS was observed in the perinuclear region. RalGDS which was targeted to the plasma membrane by the addition of Ras farnesylation site (RalGDS-CAAX) activated Ral in the absence of RasG12V. Although RalGDS did not stimulate the dissociation of GDP from Ral in the absence of the GTP-bound form of Ras in a reconstitution assay using the liposomes, RalGDS-CAAX could stimulate it without Ras. RasG12V activated Raf-1 when they were coexpressed in Sf9 cells, whereas RasG12V did not affect the RalGDS activity. These results indicate that Ras recruits RalGDS to the plasma membrane and that the translocated RalGDS induces the activation of Ral, but that Rap1 does not activate Ral due to distinct subcellular localization.
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Acknowledgements
We are grateful to Dr M Kishida, for technical assistance and Drs M Nakata and T Kataoka for the antibodies and plasmid, respectively. We wish to thank the Research Center for Molecular Medicine and Research Facilities for Laboratory Animal Sciences, Hiroshima University School of Medicine, for the use of their facilities. This work was supported by grants-in-aid for scientific research (1997, 1998) and for scientific research on priority areas (1997, 1998) from the Ministry of Education, Science and Culture, Japan, by grants from Yamanouchi Foundation for Research on Metabolic Disorders (1997, 1998), Kato Memorial Bioscience Foundation (1997), the Naito foundation (1997).
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Matsubara, K., Kishida, S., Matsuura, Y. et al. Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation. Oncogene 18, 1303–1312 (1999). https://doi.org/10.1038/sj.onc.1202425
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DOI: https://doi.org/10.1038/sj.onc.1202425
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