Abstract
Treatment of intact Rat-1 fibroblasts with epidermal growth factor (EGF) leads to rapid activation of cellular ras-encoded proteins. By using the bacterial toxin streptolysin O to permeabilize these cells, it was shown that the low basal rate at which guanine nucleotides bind to, and dissociate from, ras-encoded protein in quiescent fibroblasts was greatly accelerated by EGF treatment. Nucleotide binding to other proteins was not affected. Stimulation of nucleotide exchange on ras-encoded protein required tyrosine kinase but not phospholipase activity. EGF had no effect on total GTPase-activating protein activity. Regulation of ras-encoded protein in Rat-1 fibroblasts is therefore mediated by stimulation, either directly or indirectly, of ras-encoded protein-specific guanine nucleotide exchange factors by the EGF receptor tyrosine kinase.
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- Basu T. N., Gutmann D. H., Fletcher J. A., Glover T. W., Collins F. S., Downward J. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature. 1992 Apr 23;356(6371):713–715. doi: 10.1038/356713a0. [DOI] [PubMed] [Google Scholar]
- Bonfini L., Karlovich C. A., Dasgupta C., Banerjee U. The Son of sevenless gene product: a putative activator of Ras. Science. 1992 Jan 31;255(5044):603–606. doi: 10.1126/science.1736363. [DOI] [PubMed] [Google Scholar]
- Buday L., Seprödi J., Farkas G., Mészáros G., Romhányi T., Bánhegyi G., Mandl J., Antoni F., Faragó A. Proteolytic activation of protein kinase C in the extracts of cells treated for a short time with phorbol ester. FEBS Lett. 1987 Oct 19;223(1):15–19. doi: 10.1016/0014-5793(87)80501-x. [DOI] [PubMed] [Google Scholar]
- Burgering B. M., Medema R. H., Maassen J. A., van de Wetering M. L., van der Eb A. J., McCormick F., Bos J. L. Insulin stimulation of gene expression mediated by p21ras activation. EMBO J. 1991 May;10(5):1103–1109. doi: 10.1002/j.1460-2075.1991.tb08050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Downward J., Graves J. D., Warne P. H., Rayter S., Cantrell D. A. Stimulation of p21ras upon T-cell activation. Nature. 1990 Aug 23;346(6286):719–723. doi: 10.1038/346719a0. [DOI] [PubMed] [Google Scholar]
- Downward J. Regulatory mechanisms for ras proteins. Bioessays. 1992 Mar;14(3):177–184. doi: 10.1002/bies.950140308. [DOI] [PubMed] [Google Scholar]
- Downward J., Riehl R., Wu L., Weinberg R. A. Identification of a nucleotide exchange-promoting activity for p21ras. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5998–6002. doi: 10.1073/pnas.87.15.5998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duronio V., Welham M. J., Abraham S., Dryden P., Schrader J. W. p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1587–1591. doi: 10.1073/pnas.89.5.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gibbs J. B., Marshall M. S., Scolnick E. M., Dixon R. A., Vogel U. S. Modulation of guanine nucleotides bound to Ras in NIH3T3 cells by oncogenes, growth factors, and the GTPase activating protein (GAP). J Biol Chem. 1990 Nov 25;265(33):20437–20442. [PubMed] [Google Scholar]
- Graves J. D., Downward J., Izquierdo-Pastor M., Rayter S., Warne P. H., Cantrell D. A. The growth factor IL-2 activates p21ras proteins in normal human T lymphocytes. J Immunol. 1992 Apr 15;148(8):2417–2422. [PubMed] [Google Scholar]
- Graves J. D., Downward J., Rayter S., Warne P., Tutt A. L., Glennie M., Cantrell D. A. CD2 antigen mediated activation of the guanine nucleotide binding proteins p21ras in human T lymphocytes. J Immunol. 1991 Jun 1;146(11):3709–3712. [PubMed] [Google Scholar]
- Huang Y. K., Kung H. F., Kamata T. Purification of a factor capable of stimulating the guanine nucleotide exchange reaction of ras proteins and its effect on ras-related small molecular mass G proteins. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8008–8012. doi: 10.1073/pnas.87.20.8008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Izquierdo M., Downward J., Graves J. D., Cantrell D. A. Role of protein kinase C in T-cell antigen receptor regulation of p21ras: evidence that two p21ras regulatory pathways coexist in T cells. Mol Cell Biol. 1992 Jul;12(7):3305–3312. doi: 10.1128/mcb.12.7.3305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li B. Q., Kaplan D., Kung H. F., Kamata T. Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities. Science. 1992 Jun 5;256(5062):1456–1459. doi: 10.1126/science.1604323. [DOI] [PubMed] [Google Scholar]
- Martegani E., Vanoni M., Zippel R., Coccetti P., Brambilla R., Ferrari C., Sturani E., Alberghina L. Cloning by functional complementation of a mouse cDNA encoding a homologue of CDC25, a Saccharomyces cerevisiae RAS activator. EMBO J. 1992 Jun;11(6):2151–2157. doi: 10.1002/j.1460-2075.1992.tb05274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizuno T., Kaibuchi K., Yamamoto T., Kawamura M., Sakoda T., Fujioka H., Matsuura Y., Takai Y. A stimulatory GDP/GTP exchange protein for smg p21 is active on the post-translationally processed form of c-Ki-ras p21 and rhoA p21. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6442–6446. doi: 10.1073/pnas.88.15.6442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mulder K. M., Morris S. L. Activation of p21ras by transforming growth factor beta in epithelial cells. J Biol Chem. 1992 Mar 15;267(8):5029–5031. [PubMed] [Google Scholar]
- Muroya K., Hattori S., Nakamura S. Nerve growth factor induces rapid accumulation of the GTP-bound form of p21ras in rat pheochromocytoma PC12 cells. Oncogene. 1992 Feb;7(2):277–281. [PubMed] [Google Scholar]
- Qiu M. S., Green S. H. NGF and EGF rapidly activate p21ras in PC12 cells by distinct, convergent pathways involving tyrosine phosphorylation. Neuron. 1991 Dec;7(6):937–946. doi: 10.1016/0896-6273(91)90339-2. [DOI] [PubMed] [Google Scholar]
- Romhányi T., Seprödi J., Antoni F., Mészáros G., Buday L., Faragó A. The assay of the activity of protein kinase C with the synthetic oligopeptide substrate designed for histone kinase II. Biochim Biophys Acta. 1986 Oct 10;888(3):325–331. doi: 10.1016/0167-4889(86)90232-6. [DOI] [PubMed] [Google Scholar]
- Satoh T., Endo M., Nakafuku M., Akiyama T., Yamamoto T., Kaziro Y. Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7926–7929. doi: 10.1073/pnas.87.20.7926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Satoh T., Endo M., Nakafuku M., Nakamura S., Kaziro Y. Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5993–5997. doi: 10.1073/pnas.87.15.5993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Satoh T., Nakafuku M., Miyajima A., Kaziro Y. 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. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3314–3318. doi: 10.1073/pnas.88.8.3314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shou C., Farnsworth C. L., Neel B. G., Feig L. A. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21. Nature. 1992 Jul 23;358(6384):351–354. doi: 10.1038/358351a0. [DOI] [PubMed] [Google Scholar]
- Simon M. A., Bowtell D. D., Dodson G. S., Laverty T. R., Rubin G. M. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell. 1991 Nov 15;67(4):701–716. doi: 10.1016/0092-8674(91)90065-7. [DOI] [PubMed] [Google Scholar]
- Torti M., Marti K. B., Altschuler D., Yamamoto K., Lapetina E. G. Erythropoietin induces p21ras activation and p120GAP tyrosine phosphorylation in human erythroleukemia cells. J Biol Chem. 1992 Apr 25;267(12):8293–8298. [PubMed] [Google Scholar]
- Wei W., Mosteller R. D., Sanyal P., Gonzales E., McKinney D., Dasgupta C., Li P., Liu B. X., Broek D. Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7100–7104. doi: 10.1073/pnas.89.15.7100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- West M., Kung H. F., Kamata T. A novel membrane factor stimulates guanine nucleotide exchange reaction of ras proteins. FEBS Lett. 1990 Jan 1;259(2):245–248. doi: 10.1016/0014-5793(90)80019-f. [DOI] [PubMed] [Google Scholar]
- Wolfman A., Macara I. G. A cytosolic protein catalyzes the release of GDP from p21ras. Science. 1990 Apr 6;248(4951):67–69. doi: 10.1126/science.2181667. [DOI] [PubMed] [Google Scholar]
- Zhang K., Papageorge A. G., Lowy D. R. Mechanistic aspects of signaling through Ras in NIH 3T3 cells. Science. 1992 Jul 31;257(5070):671–674. doi: 10.1126/science.1496380. [DOI] [PubMed] [Google Scholar]