This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cai, H
Right arrow Articles by Cooper, G M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cai, H
Right arrow Articles by Cooper, G M

 Previous Article  |  Next Article 

Mol Cell Biol. 1990 October; 10(10): 5314-5323

Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.

H Cai, J Szeberényi and G M Cooper

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.

ABSTRACT

We used a dominant inhibitory mutation of c-Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21(Asn-17)Ha-ras] to investigate ras function in mitogenic signal transduction. An NIH 3T3 cell line [NIH(M17)] was isolated that displayed inducible expression of the mutant Ha-ras gene (Ha-ras Asn-17) via the mouse mammary tumor virus long terminal repeat and was growth inhibited by dexamethasone. The effect of dexamethasone induction on response of quiescent NIH(M17) cells to mitogens was then analyzed. Stimulation of DNA synthesis by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) was completely blocked by p21(Asn-17) expression, and stimulation by serum, fibroblast growth factor, and platelet-derived growth factor was partially inhibited. However, the induction of fos, jun, and myc by EGF and TPA was not significantly inhibited in this cell line. An effect of p21(Asn-17) on fos induction was, however, demonstrated in transient expression assays in which quiescent NIH 3T3 cells were cotransfected with a fos-cat receptor plasmid plus a Ha-ras Asn-17 expression vector. In this assay, p21(Asn-17) inhibited chloramphenicol acetyltransferase expression induced by EGF and other growth factors. In contrast to its effect on DNA synthesis, however, Ha-ras Asn-17 expression did not inhibit fos-cat expression induced by TPA. Conversely, downregulation of protein kinase C did not inhibit fos-cat induction by activated ras or other oncogenes. These results suggest that ras proteins are involved in at least two parallel mitogenic signal transduction pathways, one of which is independent of protein kinase C. Although either pathway alone appears to be sufficient to induce fos, both appear to be necessary to induce the full mitogenic response.

Mol Cell Biol. 1990 October; 10(10): 5314-5323




This article has been cited by other articles:

  • Tanigawa, H., Miura, S.-i., Matsuo, Y., Fujino, M., Sawamura, T., Saku, K. (2006). Dominant-Negative Lox-1 Blocks Homodimerization of Wild-Type Lox-1-Induced Cell Proliferation Through Extracellular Signal Regulated Kinase 1/2 Activation. Hypertension 48: 294-300 [Abstract] [Full Text]  
  • Yun, M.-S., Kim, S.-E., Jeon, S. H., Lee, J.-S., Choi, K.-Y. (2005). Both ERK and Wnt/{beta}-catenin pathways are involved in Wnt3a-induced proliferation. J. Cell Sci. 118: 313-322 [Abstract] [Full Text]  
  • Lepique, A. P., Moraes, M. S, Rocha, K. M, Eichler, C. B, Hajj, G. N M, Schwindt, T. T, Armelin, H. A (2004). c-Myc protein is stabilized by fibroblast growth factor 2 and destabilized by ACTH to control cell cycle in mouse Y1 adrenocortical cells. J Mol Endocrinol 33: 623-638 [Abstract] [Full Text]  
  • D'Abaco, G. M., Hooper, S., Paterson, H., Marshall, C. J. (2002). Loss of Rb overrides the requirement for ERK activity for cell proliferation. J. Cell Sci. 115: 4607-4616 [Abstract] [Full Text]  
  • Reddy, S. T., Wadleigh, D. J., Herschman, H. R. (2000). Transcriptional Regulation of the Cyclooxygenase-2 Gene in Activated Mast Cells. J. Biol. Chem. 275: 3107-3113 [Abstract] [Full Text]  
  • Boerner, J., McManus, M., Martin, G., Maihle, N. (2000). Ras-independent oncogenic transformation by an EGF-receptor mutant. J. Cell Sci. 113: 935-942 [Abstract]  
  • Band, C. J., Mounier, C., Posner, B. I. (1999). Epidermal Growth Factor and Insulin-Induced Deoxyribonucleic Acid Synthesis in Primary Rat Hepatocytes Is Phosphatidylinositol 3-Kinase Dependent and Dissociated from Protooncogene Induction. Endocrinology 140: 5626-5634 [Abstract] [Full Text]  
  • Esparza, J., Vilardell, C., Calvo, J., Juan, M., Vives, J., Urbano-Marquez, A., Yague, J., Cid, M. C. (1999). Fibronectin Upregulates Gelatinase B (MMP-9) and Induces Coordinated Expression of Gelatinase A (MMP-2) and Its Activator MT1-MMP (MMP-14) by Human T Lymphocyte Cell Lines. A Process Repressed Through RAS/MAP Kinase Signaling Pathways. Blood 94: 2754-2766 [Abstract] [Full Text]  
  • Cool, R. H., Schmidt, G., Lenzen, C. U., Prinz, H., Vogt, D., Wittinghofer, A. (1999). The Ras Mutant D119N Is Both Dominant Negative and Activated. Mol. Cell. Biol. 19: 6297-6305 [Abstract] [Full Text]  
  • Gille, H., Downward, J. (1999). Multiple Ras Effector Pathways Contribute to G1 Cell Cycle Progression. J. Biol. Chem. 274: 22033-22040 [Abstract] [Full Text]  
  • Nguyen, D. H.D., Catling, A. D., Webb, D. J., Sankovic, M., Walker, L. A., Somlyo, A. V., Weber, M. J., Gonias, S. L. (1999). Myosin Light Chain Kinase Functions Downstream of Ras/ERK to Promote Migration of Urokinase-Type Plasminogen Activator-Stimulated Cells in an Integrin-Selective Manner. JCB 146: 149-164 [Abstract] [Full Text]  
  • Adam-Stitah, S., Penna, L., Chambon, P., Rochette-Egly, C. (1999). Hyperphosphorylation of the Retinoid X Receptor alpha  by Activated c-Jun NH2-terminal Kinases. J. Biol. Chem. 274: 18932-18941 [Abstract] [Full Text]  
  • Barroso, I., Santisteban, P. (1999). Insulin-induced Early Growth Response Gene (Egr-1) Mediates a Short Term Repression of Rat Malic Enzyme Gene Transcription. J. Biol. Chem. 274: 17997-18004 [Abstract] [Full Text]  
  • Takuwa, N., Fukui, Y., Takuwa, Y. (1999). Cyclin D1 Expression Mediated by Phosphatidylinositol 3-Kinase through mTOR-p70S6K-Independent Signaling in Growth Factor-Stimulated NIH 3T3 Fibroblasts. Mol. Cell. Biol. 19: 1346-1358 [Abstract] [Full Text]  
  • Ladha, M. H., Lee, K. Y., Upton, T. M., Reed, M. F., Ewen, M. E. (1998). Regulation of Exit from Quiescence by p27 and Cyclin D1-CDK4. Mol. Cell. Biol. 18: 6605-6615 [Abstract] [Full Text]  
  • Li, J., Smithgall, T. E. (1998). Fibroblast Transformation by Fps/Fes Tyrosine Kinases Requires Ras, Rac, and Cdc42 and Induces Extracellular Signal-regulated and c-Jun N-terminal Kinase Activation. J. Biol. Chem. 273: 13828-13834 [Abstract] [Full Text]  
  • Durick, K., Gill, G. N., Taylor, S. S. (1998). Shc and Enigma Are Both Required for Mitogenic Signaling by Ret/ptc2. Mol. Cell. Biol. 18: 2298-2308 [Abstract] [Full Text]  
  • Smithgall, T. E. (1998). Signal Transduction Pathways Regulating Hematopoietic Differentiation. Pharmacol. Rev. 50: 1-20 [Abstract] [Full Text]  
  • Johnson, L., Greenbaum, D., Cichowski, K., Mercer, K., Murphy, E., Schmitt, E., Bronson, R. T., Umanoff, H., Edelmann, W., Kucherlapati, R., Jacks, T. (1997). K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev. 11: 2468-2481 [Abstract] [Full Text]  
  • Han, L., Wong, D., Dhaka, A., Afar, D., White, M., Xie, W., Herschman, H., Witte, O., Colicelli, J. (1997). Protein binding and signaling properties of RIN1 suggest a unique effector function. Proc. Natl. Acad. Sci. USA 94: 4954-4959 [Abstract] [Full Text]  
  • Ueno, H., Yamamoto, H., Ito, S.-i., Li, J.-J., Takeshita, A. (1997). Adenovirus-Mediated Transfer of a Dominant-Negative H-ras Suppresses Neointimal Formation in Balloon-Injured Arteries In Vivo. Arterioscler. Thromb. Vasc. Bio. 17: 898-904 [Abstract] [Full Text]  
  • Goillot, E., Raingeaud, J., Ranger, A., Tepper, R. I., Davis, Roger. J., Harlow, E., Sanchez, I. (1997). Mitogen-activated protein kinase-mediated Fas apoptotic signaling pathway. Proc. Natl. Acad. Sci. USA 94: 3302-3307 [Abstract] [Full Text]  
  • Mitsui, H., Takuwa, N., Kurokawa, K., Exton, J. H., Takuwa, Y. (1997). Dependence of Activated Galpha 12-induced G1 to S Phase Cell Cycle Progression on Both Ras/Mitogen-activated Protein Kinase and Ras/Rac1/Jun N-terminal Kinase Cascades in NIH3T3 Fibroblasts. J. Biol. Chem. 272: 4904-4910 [Abstract] [Full Text]  
  • Guay, J, Lambert, H, Gingras-Breton, G, Lavoie, J., Huot, J, Landry, J (1997). Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27. J. Cell Sci. 110: 357-368 [Abstract]  
  • Hartsough, M. T., Frey, R. S., Zipfel, P. A., Buard, A., Cook, S. J., McCormick, F., Mulder, K. M. (1996). Altered Transforming Growth Factor beta Signaling in Epithelial Cells when Ras Activation Is Blocked. J. Biol. Chem. 271: 22368-22375 [Abstract] [Full Text]  
  • Patten, M., Hartogensis, W. E., Long, C. S. (1996). Interleukin-1beta Is a Negative Transcriptional Regulator of alpha 1-Adrenergic Induced Gene Expression in Cultured Cardiac Myocytes. J. Biol. Chem. 271: 21134-21141 [Abstract] [Full Text]  
  • Kirstein, M., Sanz, L., Quinones, S., Moscat, J., Diaz-Meco, MariaT., Saus, J. (1996). Cross-talk between Different Enhancer Elements during Mitogenic Induction of the Human Stromelysin-1 Gene. J. Biol. Chem. 271: 18231-18236 [Abstract] [Full Text]  
  • Simonson, M. S., Wang, Y., Herman, W. H. (1996). Nuclear Signaling by Endothelin-1 Requires Src Protein-tyrosine Kinases. J. Biol. Chem. 271: 77-82 [Abstract] [Full Text]  
  • Henry, G., Brivanlou, I., Kessler, D., Hemmati-Brivanlou, A, Melton, D. (1996). TGF-beta signals and a pattern in Xenopus laevis endodermal development. Development 122: 1007-1015 [Abstract]  
  • Terada, K., Kaziro, Y., Satoh, T. (1995). Ras Is Not Required for the Interleukin 3-induced Proliferation of a Mouse Pro-B Cell Line, BaF3. J. Biol. Chem. 270: 27880-27886 [Abstract] [Full Text]  
  • Briggs, S. D., Bryant, S. S., Jove, R., Sanderson, S. D., Smithgall, T. E. (1995). The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck. J. Biol. Chem. 270: 14718-14724 [Abstract] [Full Text]  
  • Jiang, H., Lu, Z., Luo, J.-Q., Wolfman, A., Foster, D. A. (1995). Ras Mediates the Activation of Phospholipase D by v-Src. J. Biol. Chem. 270: 6006-6009 [Abstract] [Full Text]  
  • Sa, G., Murugesan, G., Jaye, M., Ivashchenko, Y., Fox, P. L. (1995). Activation of Cytosolic Phospholipase A(2) by Basic Fibroblast Growth Factor via a p42 Mitogen-activated Protein Kinase-dependent Phosphorylation Pathway in Endothelial Cells. J. Biol. Chem. 270: 2360-2366 [Abstract] [Full Text]  
  • LaBonne, C, Burke, B, Whitman, M (1995). Role of MAP kinase in mesoderm induction and axial patterning during Xenopus development. Development 121: 1475-1486 [Abstract]  
  • Hipskind, R A, Buscher, D, Nordheim, A, Baccarini, M (1994). Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors.. Genes Dev. 8: 1803-1816 [Abstract]  
  • LaBonne, C, Whitman, M (1994). Mesoderm induction by activin requires FGF-mediated intracellular signals. Development 120: 463-472 [Abstract]  
  • Van Aelst, L., White, M.A., Wigler, M.H. (1994). Ras Partners. Cold Spring Harb Symp Quant Biol 59: 181-186 [Abstract]  
  • Ravichandran, K., Lee, K., Songyang, Z, Cantley, L., Burn, P, Burakoff, S. (1993). Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation. Science 262: 902-905 [Abstract]  
  • Chardin, P, Camonis, J., Gale, N., van Aelst, L, Schlessinger, J, Wigler, M., Bar-Sagi, D (1993). Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science 260: 1338-1343 [Abstract]  
  • Bruder, J T, Heidecker, G, Rapp, U R (1992). Serum-, TPA-, and Ras-induced expression from Ap-1/Ets-driven promoters requires Raf-1 kinase.. Genes Dev. 6: 545-556 [Abstract]  
  • Benito, M, Porras, A, Nebreda, A., Santos, E (1991). Differentiation of 3T3-L1 fibroblasts to adipocytes induced by transfection of ras oncogenes. Science 253: 565-568 [Abstract]  
  • Mamon, H., Williams, N., Wood, K., Frazier, A.L., Li, P., Zmuidzinas, A., Kremer, N., D'Acangelo, G., Qi, H., Smith, K., Feig, L., Piwnica-Worms, H., Halegoua, S., Roberts, T. (1991). New Perspectives on Raf-1: The Involvement of p21ras in the Activation of Raf-1 and a Potential Role for Raf-1 in Events Occurring Later in the Cell Cycle. Cold Spring Harb Symp Quant Biol 56: 251-263 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»