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Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21

Nature volume 358, pages 351–354 (1992)Cite this article

Abstract

THE stimulation of a variety of cell surface receptors promotes the accumulation of the active, GTP-bound form of Ras proteins in cells1—4. This is a critical step in signal transduction because inhibition of Ras activation by anti-Ras antibodies or dominant inhibitory Ras mutants blocks many of the effects of these receptors on cellular function5—8. To reach the active GTP-bound state, Ras proteins must first release bound GDP. This rate-limiting step in GTP binding is thought to be catalysed by a guanine-nucleotide-releasing factor (GRF)9—11. Here we report the cloning of complementary DNAs from a rat brain library that encode a ∼140 GRF for Ras p21 (p140Ras-GRF). Its carboxy-terminal region is similar to that of CDC25, a GRF for Saccharomyces cerevisiae RAS11. This portion of Ras-GRF accelerated the release of GDP from RasH and RasN p21 in vitro, but not from the related RalA, or CDC42Hs GTP-binding proteins. A region in the a mi no-terminal end of Ras-GRF is similar to both the human breakpoint cluster protein, Bcr12, and the dbl oncogene product13, a guanine-nucleotide-releasing factor for CDC42Hs14. An understanding of Ras-GRF function will enhance our knowledge of the many signal transduction pathways mediated by Ras proteins.

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Authors and Affiliations

  1. Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA

    Chengchao Shou, Charles L. Farnsworth & Larry A. Feig

  2. Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts, 02215, USA

    Benjamin G. Neel

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  1. Chengchao Shou
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  2. Charles L. Farnsworth
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  3. Benjamin G. Neel
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  4. Larry A. Feig
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Shou, C., Farnsworth, C., Neel, B. et al. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21. Nature 358, 351–354 (1992). https://doi.org/10.1038/358351a0

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