Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21
- 1 July 1992
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 358 (6384), 351-354
- https://doi.org/10.1038/358351a0
Abstract
The stimulation of a variety of cell surface receptors promotes the accumulation of the active, GTP-bound form of Ras proteins in cells. 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 function. 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). Here we report the cloning of complementary DNAs from a rat brain library that encode a approximately 140K GRF for Ras p21 (p140Ras-GRF). Its carboxy-terminal region is similar to that of CDC25, a GRF for Saccharomyces cerevisiae RAS. 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 amino-terminal end of Ras-GRF is similar to both the human breakpoint cluster protein, Bcr, and the dbl oncogene product, a guanine-nucleotide-releasing factor for CDC42Hs. An understanding of Ras-GRF function will enhance our knowledge of the many signal transduction pathways mediated by Ras proteins.Keywords
This publication has 25 references indexed in Scilit:
- Two dominant inhibitory mutants of p21ras interfere with insulin-induced gene expression.Molecular and Cellular Biology, 1991
- Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbloncogene productNature, 1991
- The CDC25 protein of Saccharomyces cerevisiae promotes exchange of guanine nucleotides bound to ras.Molecular and Cellular Biology, 1991
- Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4.Proceedings of the National Academy of Sciences of the United States of America, 1991
- Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.Molecular and Cellular Biology, 1990
- Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.Molecular and Cellular Biology, 1990
- Stimulation of p21ras upon T-cell activationNature, 1990
- Identification of a nucleotide exchange-promoting activity for p21ras.Proceedings of the National Academy of Sciences of the United States of America, 1990
- A Cytosolic Protein Catalyzes the Release of GDP from p21
ras
Science, 1990
- Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cellsNature, 1985