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 Woods, D.
Right arrow Articles by McMahon, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woods, D.
Right arrow Articles by McMahon, M.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 09 1997, 5598-5611, Vol 17, No. 9
Copyright © 1997, American Society for Microbiology

Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1

D Woods, D Parry, H Cherwinski, E Bosch, E Lees and M McMahon
Department of Cell Signaling, DNAX Research Institute, Palo Alto, California 94304, USA.

The Raf family of protein kinases display differences in their abilities to promote the entry of quiescent NIH 3T3 cells into the S phase of the cell cycle. Although conditional activation of deltaA- Raf:ER promoted cell cycle progression, activation of deltaRaf-1:ER and deltaB-Raf:ER elicited a G1 arrest that was not overcome by exogenously added growth factors. Activation of all three deltaRaf:ER kinases led to elevated expression of cyclin D1 and cyclin E and reduced expression of p27Kip1. However, activation of deltaB-Raf:ER and deltaRaf-1:ER induced the expression of p21Cip1, whereas activation of deltaA-Raf:ER did not. A catalytically potentiated form of deltaA-Raf:ER, generated by point mutation, strongly induced p21Cip1 expression and elicited cell cycle arrest similarly to deltaB-Raf:ER and deltaRaf-1:ER. These data suggested that the strength and duration of signaling by Raf kinases might influence the biological outcome of activation of this pathway. By titration of deltaB-Raf:ER activity we demonstrated that low levels of Raf activity led to activation of cyclin D1-cdk4 and cyclin E-cdk2 complexes and to cell cycle progression whereas higher Raf activity elicited cell cycle arrest correlating with p21Cip1 induction and inhibition of cyclin-cdk activity. Using green fluorescent protein-tagged forms of deltaRaf-1:ER in primary mouse embryo fibroblasts (MEFs) we demonstrated that p21Cip1 was induced by Raf in a p53-independent manner, leading to cell cycle arrest. By contrast, activation of Raf in p21Cip1(-/-) MEFs led to a robust mitogenic response that was similar to that observed in response to platelet-derived growth factor. These data indicate that, depending on the level of kinase activity, Raf can elicit either cell cycle progression or cell cycle arrest in mouse fibroblasts. The ability of Raf to elicit cell cycle arrest is strongly associated with its ability to induce the expression of the cyclin-dependent kinase inhibitor p21Cip1 in a manner that bears analogy to alpha-factor arrest in Saccharomyces cerevisiae. These data are consistent with a role for Raf kinases in both proliferation and differentiation of mammalian cells.


This article has been cited by other articles:

  • Geest, C. R., Buitenhuis, M., Groot Koerkamp, M. J. A., Holstege, F. C. P., Vellenga, E., Coffer, P. J. (2009). Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors. Blood 114: 3402-3412 [Abstract] [Full Text]  
  • Kim, S., Nadel, J. A. (2009). Fibrinogen binding to ICAM-1 promotes EGFR-dependent mucin production in human airway epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L174-L183 [Abstract] [Full Text]  
  • Agger, K., Cloos, P. A.C., Rudkjaer, L., Williams, K., Andersen, G., Christensen, J., Helin, K. (2009). The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev. 23: 1171-1176 [Abstract] [Full Text]  
  • Matheny, S. A., White, M. A. (2009). Signaling Threshold Regulation by the Ras Effector IMP. J. Biol. Chem. 284: 11007-11011 [Abstract] [Full Text]  
  • Thaler, S., Hahnel, P. S., Schad, A., Dammann, R., Schuler, M. (2009). RASSF1A Mediates p21Cip1/Waf1-Dependent Cell Cycle Arrest and Senescence through Modulation of the Raf-MEK-ERK Pathway and Inhibition of Akt. Cancer Res. 69: 1748-1757 [Abstract] [Full Text]  
  • Rocha, A. S., Paternot, S., Coulonval, K., Dumont, J. E., Soares, P., Roger, P. P. (2008). Cyclic AMP Inhibits the Proliferation of Thyroid Carcinoma Cell Lines through Regulation of CDK4 Phosphorylation. Mol. Biol. Cell 19: 4814-4825 [Abstract] [Full Text]  
  • Cheung, M., Sharma, A., Madhunapantula, S. V., Robertson, G. P. (2008). Akt3 and Mutant V600EB-Raf Cooperate to Promote Early Melanoma Development. Cancer Res. 68: 3429-3439 [Abstract] [Full Text]  
  • Madhunapantula, S. V., Desai, D., Sharma, A., Huh, S. J., Amin, S., Robertson, G. P. (2008). PBISe, a novel selenium-containing drug for the treatment of malignant melanoma. Molecular Cancer Therapeutics 7: 1297-1308 [Abstract] [Full Text]  
  • Quinlan, M. P., Quatela, S. E., Philips, M. R., Settleman, J. (2008). Activated Kras, but Not Hras or Nras, May Initiate Tumors of Endodermal Origin via Stem Cell Expansion. Mol. Cell. Biol. 28: 2659-2674 [Abstract] [Full Text]  
  • Waiczies, S., Bendix, I., Zipp, F. (2008). Geranylgeranylation but Not GTP-Loading of Rho GTPases Determines T Cell Function. Sci Signal 1: pt3-pt3 [Abstract] [Full Text]  
  • Hellman, N. E., Spector, J., Robinson, J., Zuo, X., Saunier, S., Antignac, C., Tobias, J. W., Lipschutz, J. H. (2008). Matrix Metalloproteinase 13 (MMP13) and Tissue Inhibitor of Matrix Metalloproteinase 1 (TIMP1), Regulated by the MAPK Pathway, Are Both Necessary for Madin-Darby Canine Kidney Tubulogenesis. J. Biol. Chem. 283: 4272-4282 [Abstract] [Full Text]  
  • Sharma, S. V., Settleman, J. (2007). Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev. 21: 3214-3231 [Abstract] [Full Text]  
  • Pennington, S. R., Foster, B. J., Hawley, S. R., Jenkins, R. E., Zolle, O., White, M. R. H., McNamee, C. J., Sheterline, P., Simpson, A. W. M. (2007). Cell Shape-dependent Control of Ca2+ Influx and Cell Cycle Progression in Swiss 3T3 Fibroblasts. J. Biol. Chem. 282: 32112-32120 [Abstract] [Full Text]  
  • LaPierre, D. P., Lee, D. Y., Li, S.-Z., Xie, Y.-Z., Zhong, L., Sheng, W., Deng, Z., Yang, B. B. (2007). The Ability of Versican to Simultaneously Cause Apoptotic Resistance and Sensitivity. Cancer Res. 67: 4742-4750 [Abstract] [Full Text]  
  • Lu, R., Wang, X., Chen, Z.-F., Sun, D.-F., Tian, X.-Q., Fang, J.-Y. (2007). Inhibition of the Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway Decreases DNA Methylation in Colon Cancer Cells. J. Biol. Chem. 282: 12249-12259 [Abstract] [Full Text]  
  • Kojima, K., Konopleva, M., Samudio, I. J., Ruvolo, V., Andreeff, M. (2007). Mitogen-Activated Protein Kinase Kinase Inhibition Enhances Nuclear Proapoptotic Function of p53 in Acute Myelogenous Leukemia Cells. Cancer Res. 67: 3210-3219 [Abstract] [Full Text]  
  • Villanueva, J., Yung, Y., Walker, J. L., Assoian, R. K. (2007). ERK Activity and G1 Phase Progression: Identifying Dispensable Versus Essential Activities and Primary Versus Secondary Targets. Mol. Biol. Cell 18: 1457-1463 [Abstract] [Full Text]  
  • Dankort, D., Filenova, E., Collado, M., Serrano, M., Jones, K., McMahon, M. (2007). A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev. 21: 379-384 [Abstract] [Full Text]  
  • Tresini, M., Lorenzini, A., Torres, C., Cristofalo, V. J. (2007). Modulation of Replicative Senescence of Diploid Human Cells by Nuclear ERK Signaling. J. Biol. Chem. 282: 4136-4151 [Abstract] [Full Text]  
  • Lee, J.-H., Lee, J.-S., Kim, S.-E., Moon, B.-S., Kim, Y.-C., Lee, S.-K., Lee, S.-K., Choi, K.-Y. (2006). Tautomycetin inhibits growth of colorectal cancer cells through p21cip/WAF1 induction via the extracellular signal-regulated kinase pathway. Molecular Cancer Therapeutics 5: 3222-3231 [Abstract] [Full Text]  
  • Houle, C. D., Ton, T.-V. T., Clayton, N., Huff, J., Hong, H.-H. L., Sills, R. C. (2006). Frequent p53 and H-ras Mutations in Benzene- and Ethylene Oxide-Induced Mammary Gland Carcinomas from B6C3F1 Mice. Toxicol Pathol 34: 752-762 [Abstract] [Full Text]  
  • Dumaz, N., Hayward, R., Martin, J., Ogilvie, L., Hedley, D., Curtin, J. A., Bastian, B. C., Springer, C., Marais, R. (2006). In Melanoma, RAS Mutations Are Accompanied by Switching Signaling from BRAF to CRAF and Disrupted Cyclic AMP Signaling. Cancer Res. 66: 9483-9491 [Abstract] [Full Text]  
  • Stehr, W., Bernal, N. P., Erwin, C. R., Bernabe, K. Q., Guo, J., Warner, B. W. (2006). Roles for p21waf1/cip1 and p27kip1 during the adaptation response to massive intestinal resection. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G933-G941 [Abstract] [Full Text]  
  • Dekanty, A., Sauane, M., Cadenas, B., Coluccio, F., Barrio, M., Casala, J., Paciencia, M., Rogers, F., Coso, O. A., Piwien-Pilipuk, G., Rudland, P. S., de Asua, L. J. (2006). Leukemia Inhibitory Factor Induces DNA Synthesis in Swiss Mouse 3T3 Cells Independently of Cyclin D1 Expression through a Mechanism Involving MEK/ERK1/2 Activation. J. Biol. Chem. 281: 6136-6143 [Abstract] [Full Text]  
  • Kortum, R. L., Johnson, H. J., Costanzo, D. L., Volle, D. J., Razidlo, G. L., Fusello, A. M., Shaw, A. S., Lewis, R. E. (2006). The Molecular Scaffold Kinase Suppressor of Ras 1 Is a Modifier of RasV12-Induced and Replicative Senescence.. Mol. Cell. Biol. 26: 2202-2214 [Abstract] [Full Text]  
  • Kalesnikoff, J., Rios, E. J., Chen, C.-C., Nakae, S., Zabel, B. A., Butcher, E. C., Tsai, M., Tam, S.-Y., Galli, S. J. (2006). RabGEF1 regulates stem cell factor/c-Kit-mediated signaling events and biological responses in mast cells.. Proc. Natl. Acad. Sci. USA 103: 2659-2664 [Abstract] [Full Text]  
  • Mercer, K., Giblett, S., Green, S., Lloyd, D., DaRocha Dias, S., Plumb, M., Marais, R., Pritchard, C. (2005). Expression of Endogenous Oncogenic V600EB-raf Induces Proliferation and Developmental Defects in Mice and Transformation of Primary Fibroblasts. Cancer Res. 65: 11493-11500 [Abstract] [Full Text]  
  • Tomlinson, D. C., L'Hote, C. G., Kennedy, W., Pitt, E., Knowles, M. A. (2005). Alternative Splicing of Fibroblast Growth Factor Receptor 3 Produces a Secreted Isoform That Inhibits Fibroblast Growth Factor-Induced Proliferation and Is Repressed in Urothelial Carcinoma Cell Lines. Cancer Res. 65: 10441-10449 [Abstract] [Full Text]  
  • Wang, X., Li, N., Li, H., Liu, B., Qiu, J., Chen, T., Cao, X. (2005). Silencing of Human Phosphatidylethanolamine-Binding Protein 4 Sensitizes Breast Cancer Cells to Tumor Necrosis Factor-{alpha}-Induced Apoptosis and Cell Growth Arrest. Clin. Cancer Res. 11: 7545-7553 [Abstract] [Full Text]  
  • Han, J., Tsukada, Y.-i., Hara, E., Kitamura, N., Tanaka, T. (2005). Hepatocyte Growth Factor Induces Redistribution of p21CIP1 and p27KIP1 through ERK-dependent p16INK4a Up-regulation, Leading to Cell Cycle Arrest at G1 in HepG2 Hepatoma Cells. J. Biol. Chem. 280: 31548-31556 [Abstract] [Full Text]  
  • Macleod, K., Mullen, P., Sewell, J., Rabiasz, G., Lawrie, S., Miller, E., Smyth, J. F., Langdon, S. P. (2005). Altered ErbB Receptor Signaling and Gene Expression in Cisplatin-Resistant Ovarian Cancer. Cancer Res. 65: 6789-6800 [Abstract] [Full Text]  
  • Gao, C.-F., Xie, Q., Su, Y.-L., Koeman, J., Khoo, S. K., Gustafson, M., Knudsen, B. S., Hay, R., Shinomiya, N., Woude, G. F. V. (2005). Proliferation and invasion: Plasticity in tumor cells. Proc. Natl. Acad. Sci. USA 102: 10528-10533 [Abstract] [Full Text]  
  • Ebisuya, M., Kondoh, K., Nishida, E. (2005). The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. J. Cell Sci. 118: 2997-3002 [Abstract] [Full Text]  
  • MacKeigan, J. P., Murphy, L. O., Dimitri, C. A., Blenis, J. (2005). Graded Mitogen-Activated Protein Kinase Activity Precedes Switch-Like c-Fos Induction in Mammalian Cells. Mol. Cell. Biol. 25: 4676-4682 [Abstract] [Full Text]  
  • Gysin, S., Lee, S.-H., Dean, N. M., McMahon, M. (2005). Pharmacologic Inhibition of RAF->MEK->ERK Signaling Elicits Pancreatic Cancer Cell Cycle Arrest Through Induced Expression of p27Kip1. Cancer Res. 65: 4870-4880 [Abstract] [Full Text]  
  • Van Gompel, J. J., Kunnimalaiyaan, M., Holen, K., Chen, H. (2005). ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. Molecular Cancer Therapeutics 4: 910-917 [Abstract] [Full Text]  
  • Waiczies, S., Prozorovski, T., Infante-Duarte, C., Hahner, A., Aktas, O., Ullrich, O., Zipp, F. (2005). Atorvastatin Induces T Cell Anergy via Phosphorylation of ERK1. J. Immunol. 174: 5630-5635 [Abstract] [Full Text]  
  • Kometiani, P., Liu, L., Askari, A. (2005). Digitalis-Induced Signaling by Na+/K+-ATPase in Human Breast Cancer Cells. Mol. Pharmacol. 67: 929-936 [Abstract] [Full Text]  
  • Trost, T. M., Lausch, E. U., Fees, S. A., Schmitt, S., Enklaar, T., Reutzel, D., Brixel, L. R., Schmidtke, P., Maringer, M., Schiffer, I. B., Heimerdinger, C. K., Hengstler, J. G., Fritz, G., Bockamp, E. O., Prawitt, D., Zabel, B. U., Spangenberg, C. (2005). Premature Senescence Is a Primary Fail-safe Mechanism of ERBB2-Driven Tumorigenesis in Breast Carcinoma Cells. Cancer Res. 65: 840-849 [Abstract] [Full Text]  
  • Croft, D. R., Coleman, M. L., Li, S., Robertson, D., Sullivan, T., Stewart, C. L., Olson, M. F. (2005). Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration. JCB 168: 245-255 [Abstract] [Full Text]  
  • Vaque, J. P., Navascues, J., Shiio, Y., Laiho, M., Ajenjo, N., Mauleon, I., Matallanas, D., Crespo, P., Leon, J. (2005). Myc Antagonizes Ras-mediated Growth Arrest in Leukemia Cells through the Inhibition of the Ras-ERK-p21Cip1 Pathway. J. Biol. Chem. 280: 1112-1122 [Abstract] [Full Text]  
  • Sreeramaneni, R., Chaudhry, A., McMahon, M., Sherr, C. J., Inoue, K. (2005). Ras-Raf-Arf Signaling Critically Depends on the Dmp1 Transcription Factor. Mol. Cell. Biol. 25: 220-232 [Abstract] [Full Text]  
  • Ambesi, A., Klein, R. M., Pumiglia, K. M., McKeown-Longo, P. J. (2005). Anastellin, a Fragment of the First Type III Repeat of Fibronectin, Inhibits Extracellular Signal-Regulated Kinase and Causes G1 Arrest in Human Microvessel Endothelial Cells. Cancer Res. 65: 148-156 [Abstract] [Full Text]  
  • Mirza, A. M., Gysin, S., Malek, N., Nakayama, K.-i., Roberts, J. M., McMahon, M. (2004). Cooperative Regulation of the Cell Division Cycle by the Protein Kinases RAF and AKT. Mol. Cell. Biol. 24: 10868-10881 [Abstract] [Full Text]  
  • Foulds, C. E., Nelson, M. L., Blaszczak, A. G., Graves, B. J. (2004). Ras/Mitogen-Activated Protein Kinase Signaling Activates Ets-1 and Ets-2 by CBP/p300 Recruitment. Mol. Cell. Biol. 24: 10954-10964 [Abstract] [Full Text]  
  • Yang, G., Cao, K., Wu, L., Wang, R. (2004). Cystathionine {gamma}-Lyase Overexpression Inhibits Cell Proliferation via a H2S-dependent Modulation of ERK1/2 Phosphorylation and p21Cip/WAK-1. J. Biol. Chem. 279: 49199-49205 [Abstract] [Full Text]  
  • Ussar, S., Voss, T. (2004). MEK1 and MEK2, Different Regulators of the G1/S Transition. J. Biol. Chem. 279: 43861-43869 [Abstract] [Full Text]  
  • Ricci, M. S., Jin, Z., Dews, M., Yu, D., Thomas-Tikhonenko, A., Dicker, D. T., El-Deiry, W. S. (2004). Direct Repression of FLIP Expression by c-myc Is a Major Determinant of TRAIL Sensitivity. Mol. Cell. Biol. 24: 8541-8555 [Abstract] [Full Text]  
  • Wu, J., Wong, W. W.-L., Khosravi, F., Minden, M. D., Penn, L. Z. (2004). Blocking the Raf/MEK/ERK Pathway Sensitizes Acute Myelogenous Leukemia Cells to Lovastatin-Induced Apoptosis. Cancer Res. 64: 6461-6468 [Abstract] [Full Text]  
  • Scholl, F. A., Dumesic, P. A., Khavari, P. A. (2004). Mek1 Alters Epidermal Growth and Differentiation. Cancer Res. 64: 6035-6040 [Abstract] [Full Text]  
  • Dorrell, C., Takenaka, K., Minden, M. D., Hawley, R. G., Dick, J. E. (2004). Hematopoietic Cell Fate and the Initiation of Leukemic Properties in Primitive Primary Human Cells Are Influenced by Ras Activity and Farnesyltransferase Inhibition. Mol. Cell. Biol. 24: 6993-7002 [Abstract] [Full Text]  
  • Mizuno, S., Kadowaki, M., Demura, Y., Ameshima, S., Miyamori, I., Ishizaki, T. (2004). p42/44 Mitogen-Activated Protein Kinase Regulated by p53 and Nitric Oxide in Human Pulmonary Arterial Smooth Muscle Cells. Am. J. Respir. Cell Mol. Bio. 31: 184-192 [Abstract] [Full Text]  
  • Schulze, A., Nicke, B., Warne, P. H., Tomlinson, S., Downward, J. (2004). The Transcriptional Response to Raf Activation Is Almost Completely Dependent on Mitogen-activated Protein Kinase Kinase Activity and Shows a Major Autocrine Component. Mol. Biol. Cell 15: 3450-3463 [Abstract] [Full Text]  
  • Rodriguez-Viciana, P., Sabatier, C., McCormick, F. (2004). Signaling Specificity by Ras Family GTPases Is Determined by the Full Spectrum of Effectors They Regulate. Mol. Cell. Biol. 24: 4943-4954 [Abstract] [Full Text]  
  • Maldonado, J. L., Timmerman, L., Fridlyand, J., Bastian, B. C. (2004). Mechanisms of Cell-Cycle Arrest in Spitz Nevi with Constitutive Activation of the MAP-Kinase Pathway. Am. J. Pathol. 164: 1783-1787 [Abstract] [Full Text]  
  • Hager, J. H., Hodgson, J. G., Fridlyand, J., Hariono, S., Gray, J. W., Hanahan, D. (2004). Oncogene Expression and Genetic Background Influence the Frequency of DNA Copy Number Abnormalities in Mouse Pancreatic Islet Cell Carcinomas. Cancer Res. 64: 2406-2410 [Abstract] [Full Text]  
  • Liu, W., Shen, X., Yang, Y., Yin, X., Xie, J., Yan, J., Jiang, J., Liu, W., Wang, H., Sun, M., Zheng, Y., Gu, J. (2004). Trihydrophobin 1 Is a New Negative Regulator of A-Raf Kinase. J. Biol. Chem. 279: 10167-10175 [Abstract] [Full Text]  
  • Clark, J. A., Black, A. R., Leontieva, O. V., Frey, M. R., Pysz, M. A., Kunneva, L., Woloszynska-Read, A., Roy, D., Black, J. D. (2004). Involvement of the ERK Signaling Cascade in Protein Kinase C-mediated Cell Cycle Arrest in Intestinal Epithelial Cells. J. Biol. Chem. 279: 9233-9247 [Abstract] [Full Text]  
  • Lawson, B. R., Baccala, R., Song, J., Croft, M., Kono, D. H., Theofilopoulos, A. N. (2004). Deficiency of the Cyclin Kinase Inhibitor p21(WAF-1/CIP-1) Promotes Apoptosis of Activated/Memory T Cells and Inhibits Spontaneous Systemic Autoimmunity. JEM 199: 547-557 [Abstract] [Full Text]  
  • Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., Scrable, H. (2004). Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18: 306-319 [Abstract] [Full Text]  
  • Raucci, A., Laplantine, E., Mansukhani, A., Basilico, C. (2004). Activation of the ERK1/2 and p38 Mitogen-activated Protein Kinase Pathways Mediates Fibroblast Growth Factor-induced Growth Arrest of Chondrocytes. J. Biol. Chem. 279: 1747-1756 [Abstract] [Full Text]  
  • Deng, Q., Liao, R., Wu, B.-L., Sun, P. (2004). High Intensity ras Signaling Induces Premature Senescence by Activating p38 Pathway in Primary Human Fibroblasts. J. Biol. Chem. 279: 1050-1059 [Abstract] [Full Text]  
  • Balmanno, K., Millar, T., McMahon, M., Cook, S. J. (2003). {Delta}Raf-1:ER* Bypasses the Cyclic AMP Block of Extracellular Signal-Regulated Kinase 1 and 2 Activation but Not CDK2 Activation or Cell Cycle Reentry. Mol. Cell. Biol. 23: 9303-9317 [Abstract] [Full Text]  
  • Man, A. K., Young, L. J. T., Tynan, J. A., Lesperance, J., Egeblad, M., Werb, Z., Hauser, C. A., Muller, W. J., Cardiff, R. D., Oshima, R. G. (2003). Ets2-Dependent Stromal Regulation of Mouse Mammary Tumors. Mol. Cell. Biol. 23: 8614-8625 [Abstract] [Full Text]  
  • Park, K.-S., Lee, N.-G., Lee, K.-H., Seo, J. T., Choi, K.-Y. (2003). The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G1181-G1188 [Abstract] [Full Text]  
  • Nyunoya, T., Powers, L. S., Yarovinsky, T. O., Butler, N. S., Monick, M. M., Hunninghake, G. W. (2003). Hyperoxia Induces Macrophage Cell Cycle Arrest by Adhesion-dependent Induction of p21Cip1 and Activation of the Retinoblastoma Protein. J. Biol. Chem. 278: 36099-36106 [Abstract] [Full Text]  
  • James, R. D., Jones, D. A., Aalbersberg, W., Ireland, C. M. (2003). Naamidine A Intensifies the Phosphotransferase Activity of Extracellular Signal-regulated Kinases Causing A-431 Cells to Arrest in G1. Molecular Cancer Therapeutics 2: 747-751 [Abstract] [Full Text]  
  • Dong, J., Phelps, R. G., Qiao, R., Yao, S., Benard, O., Ronai, Z., Aaronson, S. A. (2003). BRAF Oncogenic Mutations Correlate with Progression rather than Initiation of Human Melanoma. Cancer Res. 63: 3883-3885 [Abstract] [Full Text]  
  • Sippel, R. S., Carpenter, J. E., Kunnimalaiyaan, M., Lagerholm, S., Chen, H. (2003). Raf-1 activation suppresses neuroendocrine marker and hormone levels in human gastrointestinal carcinoid cells. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G245-G254 [Abstract] [Full Text]  
  • Ostrovsky, O., Bengal, E. (2003). The Mitogen-activated Protein Kinase Cascade Promotes Myoblast Cell Survival by Stabilizing the Cyclin-dependent Kinase Inhibitor, p21WAF1 Protein. J. Biol. Chem. 278: 21221-21231 [Abstract] [Full Text]  
  • Ley, R., Balmanno, K., Hadfield, K., Weston, C., Cook, S. J. (2003). Activation of the ERK1/2 Signaling Pathway Promotes Phosphorylation and Proteasome-dependent Degradation of the BH3-only Protein, Bim. J. Biol. Chem. 278: 18811-18816 [Abstract] [Full Text]  
  • Li, J., Li, W. X. (2003). Drosophila Gain-of-Function Mutant RTK Torso Triggers Ectopic Dpp and STAT Signaling. Genetics 164: 247-258 [Abstract] [Full Text]  
  • Dhillon, A. S., Meikle, S., Peyssonnaux, C., Grindlay, J., Kaiser, C., Steen, H., Shaw, P. E., Mischak, H., Eychene, A., Kolch, W. (2003). A Raf-1 Mutant That Dissociates MEK/Extracellular Signal-Regulated Kinase Activation from Malignant Transformation and Differentiation but Not Proliferation. Mol. Cell. Biol. 23: 1983-1993 [Abstract] [Full Text]  
  • Li, W. X., Agaisse, H., Mathey-Prevot, B., Perrimon, N. (2003). Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila. Development 129: 4241-4248 [Abstract] [Full Text]  
  • Subramaniam, S., Strelau, J., Unsicker, K. (2003). Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK Pathways. J. Biol. Chem. 278: 8904-8912 [Abstract] [Full Text]  
  • Kapoor, G. S., Golden, C., Atkins, B., Mehta, K. D. (2003). pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells. J. Lipid Res. 44: 584-593 [Abstract] [Full Text]  
  • Nicolas, F. J., Lehmann, K., Warne, P. H., Hill, C. S., Downward, J. (2003). Epithelial to Mesenchymal Transition in Madin-Darby Canine Kidney Cells Is Accompanied by Down-regulation of Smad3 Expression, Leading to Resistance to Transforming Growth Factor-beta -induced Growth Arrest. J. Biol. Chem. 278: 3251-3256 [Abstract] [Full Text]  
  • Park, J.-I., Strock, C. J., Ball, D. W., Nelkin, B. D. (2003). The Ras/Raf/MEK/Extracellular Signal-Regulated Kinase Pathway Induces Autocrine-Paracrine Growth Inhibition via the Leukemia Inhibitory Factor/JAK/STAT Pathway. Mol. Cell. Biol. 23: 543-554 [Abstract] [Full Text]  
  • Huang, Z.-y., Wu, Y., Hedrick, N., Gutmann, D. H. (2003). T-Cadherin-Mediated Cell Growth Regulation Involves G2 Phase Arrest and Requires p21CIP1/WAF1 Expression. Mol. Cell. Biol. 23: 566-578 [Abstract] [Full Text]  
  • Tarutani, M., Cai, T., Dajee, M., Khavari, P. A. (2003). Inducible Activation of Ras and Raf in Adult Epidermis. Cancer Res. 63: 319-323 [Abstract] [Full Text]  
  • Naoki, K., Chen, T.-H., Richards, W. G., Sugarbaker, D. J., Meyerson, M. (2002). Missense Mutations of the BRAF Gene in Human Lung Adenocarcinoma. Cancer Res. 62: 7001-7003 [Abstract] [Full Text]  
  • Westbrook, T. F., Nguyen, D. X., Thrash, B. R., McCance, D. J. (2002). E7 Abolishes Raf-Induced Arrest via Mislocalization of p21Cip1. Mol. Cell. Biol. 22: 7041-7052 [Abstract] [Full Text]  
  • Dixon, B. S., Evanoff, D., Fang, W. B., Dennis, M. J. (2002). Bradykinin B1 receptor blocks PDGF-induced mitogenesis by prolonging ERK activation and increasing p27Kip1. Am. J. Physiol. Cell Physiol. 283: C193-C203 [Abstract] [Full Text]  
  • Tang, D., Wu, D., Hirao, A., Lahti, J. M., Liu, L., Mazza, B., Kidd, V. J., Mak, T. W., Ingram, A. J. (2002). ERK Activation Mediates Cell Cycle Arrest and Apoptosis after DNA Damage Independently of p53. J. Biol. Chem. 277: 12710-12717 [Abstract] [Full Text]  
  • De Ruiter, N. D., Burgering, B. M. T., Bos, J. L. (2001). Regulation of the Forkhead Transcription Factor AFX by Ral-Dependent Phosphorylation of Threonines 447 and 451. Mol. Cell. Biol. 21: 8225-8235 [Abstract] [Full Text]  
  • Bottazzi, M. E., Buzzai, M., Zhu, X., Desdouets, C., Brechot, C., Assoian, R. K. (2001). Distinct Effects of Mitogens and the Actin Cytoskeleton on CREB and Pocket Protein Phosphorylation Control the Extent and Timing of Cyclin A Promoter Activity. Mol. Cell. Biol. 21: 7607-7616 [Abstract] [Full Text]  
  • Villalonga, P., Lopez-Alcala, C., Bosch, M., Chiloeches, A., Rocamora, N., Gil, J., Marais, R., Marshall, C. J., Bachs, O., Agell, N. (2001). Calmodulin Binds to K-Ras, but Not to H- or N-Ras, and Modulates Its Downstream Signaling. Mol. Cell. Biol. 21: 7345-7354 [Abstract] [Full Text]  
  • Zugasti, O., Rul, W., Roux, P., Peyssonnaux, C., Eychene, A., Franke, T. F., Fort, P., Hibner, U. (2001). Raf-MEK-Erk Cascade in Anoikis Is Controlled by Rac1 and Cdc42 via Akt. Mol. Cell. Biol. 21: 6706-6717 [Abstract] [Full Text]  
  • Carreras, I., Rich, C. B., Jaworski, J. A., Dicamillo, S. J., Panchenko, M. P., Goldstein, R., Foster, J. A. (2001). Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression. Am. J. Physiol. Lung Cell. Mol. Physiol. 281: L766-L775 [Abstract] [Full Text]  
  • Murakami, M. S., Morrison, D. K. (2001). Raf-1 Without MEK?. Sci Signal 2001: pe30-pe30 [Abstract] [Full Text]  
  • Martin-Caballero, J., Flores, J. M., Garcia-Palencia, P., Serrano, M. (2001). Tumor Susceptibility of p21Waf1/Cip1-deficient Mice. Cancer Res. 61: 6234-6238 [Abstract] [Full Text]  
  • Sonoda, Y., Ozawa, T., Hirose, Y., Aldape, K. D., McMahon, M., Berger, M. S., Pieper, R. O. (2001). Formation of Intracranial Tumors by Genetically Modified Human Astrocytes Defines Four Pathways Critical in the Development of Human Anaplastic Astrocytoma. Cancer Res. 61: 4956-4960 [Abstract] [Full Text]  
  • Schmitt, J. M., Stork, P. J. S. (2001). Cyclic AMP-Mediated Inhibition of Cell Growth Requires the Small G Protein Rap1. Mol. Cell. Biol. 21: 3671-3683 [Abstract] [Full Text]  
  • Woods, D., Cherwinski, H., Venetsanakos, E., Bhat, A., Gysin, S., Humbert, M., Bray, P. F., Saylor, V. L., McMahon, M. (2001). Induction of {beta}3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf-MEK-Extracellular Signal-Regulated Kinase Signaling Pathway. Mol. Cell. Biol. 21: 3192-3205 [Abstract] [Full Text]  
  • Richards, J. D., Dave, S. H., Chou, C.-H. G., Mamchak, A. A., DeFranco, A. L. (2001). Inhibition of the MEK/ERK Signaling Pathway Blocks a Subset of B Cell Responses to Antigen. J. Immunol. 166: 3855-3864 [Abstract] [Full Text]  
  • Hansen, S. H., Zegers, M. M. P., Woodrow, M., Rodriguez-Viciana, P., Chardin, P., Mostov, K. E., McMahon, M. (2000). Induced Expression of Rnd3 Is Associated with Transformation of Polarized Epithelial Cells by the Raf-MEK-Extracellular Signal-Regulated Kinase Pathway. Mol. Cell. Biol. 20: 9364-9375 [Abstract] [Full Text]  
  • LaMontagne, K. R. Jr., Moses, M. A., Wiederschain, D., Mahajan, S., Holden, J., Ghazizadeh, H., Frank, D. A., Arbiser, J. L. (2000). Inhibition of MAP Kinase Kinase Causes Morphological Reversion and Dissociation between Soft Agar Growth and in Vivo Tumorigenesis in Angiosarcoma Cells. Am. J. Pathol. 157: 1937-1945 [Abstract] [Full Text]  
  • WILKINSON, M. G., MILLAR, J. B. A. (2000). Control of the eukaryotic cell cycle by MAP kinase signaling pathways. FASEB J. 14: 2147-2157 [Abstract] [Full Text]  
  • Lehmann, K., Janda, E., Pierreux, C. E., Rytömaa, M., Schulze, A., McMahon, M., Hill, C. S., Beug, H., Downward, J. (2000). Raf induces TGFbeta production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes Dev. 14: 2610-2622 [Abstract] [Full Text]  
  • Peyssonnaux, C., Provot, S., Felder-Schmittbuhl, M. P., Calothy, G., Eychène, A. (2000). Induction of Postmitotic Neuroretina Cell Proliferation by Distinct Ras Downstream Signaling Pathways. Mol. Cell. Biol. 20: 7068-7079 [Abstract] [Full Text]