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B-Raf-dependent regulation of the MEK-1/mitogen-activated protein kinase pathway in PC12 cells and regulation by cyclic AMP.

Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.

ABSTRACT

Growth factor receptor tyrosine kinase regulation of the sequential phosphorylation reactions leading to mitogen-activated protein (MAP) kinase activation in PC12 cells has been investigated. In response to epidermal growth factor, nerve growth factor, and platelet-derived growth factor, B-Raf and Raf-1 are activated, phosphorylate recombinant kinase-inactive MEK-1, and activate wild-type MEK-1. MEK-1 is the dual-specificity protein kinase that selectively phosphorylates MAP kinase on tyrosine and threonine, resulting in MAP kinase activation. B-Raf and Raf-1 are growth factor-regulated Raf family members which regulate MEK-1 and MAP kinase activity in PC12 cells. Protein kinase A activation in response to elevated cyclic AMP (cAMP) levels inhibited B-Raf and Raf-1 stimulation in response to growth factors. Ras.GTP loading in response to epidermal growth factor, nerve growth factor, or platelet-derived growth factor was unaffected by protein kinase A activation. Even though elevated cAMP levels inhibited Raf activation, the growth factor activation of MEK-1 and MAP kinase was unaffected in PC12 cells. The results demonstrate that tyrosine kinase receptor activation of MEK-1 and MAP kinase in PC12 cells is regulated by B-Raf and Raf-1, whose activation is inhibited by protein kinase A, and MEK activators, whose activation is independent of cAMP regulation.

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• Fujita, T., Meguro, T., Fukuyama, R., Nakamuta, H., Koida, M. (2002). New Signaling Pathway for Parathyroid Hormone and Cyclic AMP Action on Extracellular-regulated Kinase and Cell Proliferation in Bone Cells. CHECKPOINT OF MODULATION BY CYCLIC AMP. J. Biol. Chem. 277: 22191-22200 [Abstract] [Full Text]  
• Orlic, T., Loomis, W. H., Shreve, A., Namiki, S., Junger, W. G. (2002). Hypertonicity increases cAMP in PMN and blocks oxidative burst by PKA-dependent and -independent mechanisms. Am. J. Physiol. Cell Physiol. 282: C1261-C1269 [Abstract] [Full Text]  
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• Houslay, M. D., Kolch, W. (2000). Cell-Type Specific Integration of Cross-Talk between Extracellular Signal-Regulated Kinase and cAMP Signaling. Mol. Pharmacol. 58: 659-668 [Full Text]  
• Deng, J., Chen, Y., Wu, R. (2000). Induction of Cell Cornification and Enhanced Squamous-Cell Marker SPRR1 Gene Expression by Phorbol Ester Are Regulated by Different Signaling Pathways in Human Conducting Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 22: 597-603 [Abstract] [Full Text]  
• Antonelli, V., Bernasconi, F., Wong, Y. H., Vallar, L. (2000). Activation of B-Raf and Regulation of the Mitogen-activated Protein Kinase Pathway by the Go alpha chain. Mol. Biol. Cell 11: 1129-1142 [Abstract] [Full Text]  
• MacNicol, M. C., MacNicol, A. M. (1999). Nerve Growth Factor-stimulated B-Raf Catalytic Activity Is Refractory to Inhibition by cAMP-dependent Protein Kinase. J. Biol. Chem. 274: 13193-13197 [Abstract] [Full Text]  
• Kartha, S., Naureckas, E. T., Li, J., Hershenson, M. B. (1999). Partial Characterization of a Novel Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Activator in Airway Smooth-Muscle Cells. Am. J. Respir. Cell Mol. Bio. 20: 1041-1048 [Abstract] [Full Text]  
• Florio, T., Yao, H., Carey, K. D., Dillon, T. J., Stork, P. J. S. (1999). Somatostatin Activation of Mitogen-Activated Protein Kinase via Somatostatin Receptor 1 (SSTR1). Mol. Endocrinol. 13: 24-37 [Abstract] [Full Text]  
• Chen, T., Cho, R. W., Stork, P. J. S., Weber, M. J. (1999). Elevation of Cyclic Adenosine 3',5'-Monophosphate Potentiates Activation of Mitogen-activated Protein Kinase by Growth Factors in LNCaP Prostate Cancer Cells. Cancer Res. 59: 213-218 [Abstract] [Full Text]  
• WIDMANN, C., GIBSON, S., JARPE, M. B., JOHNSON, G. L. (1999). Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev. 79: 143-180 [Abstract] [Full Text]  
• Suhasini, M., Li, H., Lohmann, S. M., Boss, G. R., Pilz, R. B. (1998). Cyclic-GMP-Dependent Protein Kinase Inhibits the Ras/Mitogen-Activated Protein Kinase Pathway. Mol. Cell. Biol. 18: 6983-6994 [Abstract] [Full Text]  
• Rahmatullah, M., Schroering, A., Rothblum, K., Stahl, R. C., Urban, B., Carey, D. J. (1998). Synergistic Regulation of Schwann Cell Proliferation by Heregulin and Forskolin. Mol. Cell. Biol. 18: 6245-6252 [Abstract] [Full Text]  
• Miller, M. J., Rioux, L., Prendergast, G. V., Cannon, S., White, M. A., Meinkoth, J. L. (1998). Differential Effects of Protein Kinase A on Ras Effector Pathways. Mol. Cell. Biol. 18: 3718-3726 [Abstract] [Full Text]  
• Benes, C., Roisin, M. P., Van Tan, H., Creuzet, C., Miyazaki, J.-i., Fagard, R. (1998). Rapid Activation and Nuclear Translocation of Mitogen-activated Protein Kinases in Response to Physiological Concentration of Glucose in the MIN6 Pancreatic beta  Cell Line. J. Biol. Chem. 273: 15507-15513 [Abstract] [Full Text]  
• Lee, Y. J., Galoforo, S. S., Berns, C. M., Chen, J. C., Davis, B. H., Sim, J. E., Corry, P. M., Spitz, D. R. (1998). Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells. J. Biol. Chem. 273: 5294-5299 [Abstract] [Full Text]  
• Li, Y., Lau, L. F. (1997). Adrenocorticotropic Hormone Regulates the Activities of the Orphan Nuclear Receptor Nur77 through Modulation of Phosphorylation. Endocrinology 138: 4138-4146 [Abstract] [Full Text]  
• Schramek, H., Feifel, E., Healy, E., Pollack, V. (1997). Constitutively Active Mutant of the Mitogen-activated Protein Kinase Kinase MEK1 Induces Epithelial Dedifferentiation and Growth Inhibition in Madin-Darby Canine Kidney-C7 Cells. J. Biol. Chem. 272: 11426-11433 [Abstract] [Full Text]  
• Calleja, V., Ruiz Enriquez, P., Filloux, C., Peraldi, P., Baron, V., Van Obberghen, E. (1997). The Effect of Cyclic Adenosine Monophosphate on the Mitogen-Activated Protein Kinase Pathway Depends on Both the Cell Type and the Type of Tyrosine Kinase-Receptor. Endocrinology 138: 1111-1120 [Abstract] [Full Text]  
• Cioffi, C. L., Garay, M., Johnston, J. F., McGraw, K., Boggs, R. T., Hreniuk, D., Monia, B. P. (1997). Selective Inhibition of A-Raf and C-Raf mRNA Expression by Antisense Oligodeoxynucleotides in Rat Vascular Smooth Muscle Cells: Role of A-Raf and C-Raf in Serum-Induced Proliferation. Mol. Pharmacol. 51: 383-389 [Abstract] [Full Text]  
• Miller, M. J., Prigent, S., Kupperman, E., Rioux, L., Park, S.-H., Feramisco, J. R., White, M. A., Rutkowski, J. L., Meinkoth, J. L. (1997). RalGDS Functions in Ras- and cAMP-mediated Growth Stimulation. J. Biol. Chem. 272: 5600-5605 [Abstract] [Full Text]  
• Verheijen, M. H.G., Defize, L. H.K. (1997). Parathyroid Hormone Activates Mitogen-activated Protein Kinase via a cAMP-mediated Pathway Independent of Ras. J. Biol. Chem. 272: 3423-3429 [Abstract] [Full Text]  
• Liao, D.-F., Duff, J. L., Daum, G., Pelech, S. L., Berk, B. C. (1996). Angiotensin II Stimulates MAP Kinase Kinase Kinase Activity in Vascular Smooth Muscle Cells: Role of Raf. Circ. Res. 79: 1007-1014 [Abstract] [Full Text]  
• Jaiswal, R. K., Weissinger, E., Kolch, W., Landreth, G. E. (1996). Nerve Growth Factor-mediated Activation of the Mitogen-activated Protein (MAP) Kinase Cascade Involves a Signaling Complex Containing B-Raf and HSP90. J. Biol. Chem. 271: 23626-23629 [Abstract] [Full Text]  
• Creedon, D. J., Johnson, E. M. Jr., Lawrence, J. C. Jr. (1996). Mitogen-activated Protein Kinase-independent Pathways Mediate the Effects of Nerve Growth Factor and cAMP on Neuronal Survival. J. Biol. Chem. 271: 20713-20718 [Abstract] [Full Text]  
• Servant, M. J., Giasson, E., Meloche, S. (1996). Inhibition of Growth Factor-induced Protein Synthesis by a Selective MEK Inhibitor in Aortic Smooth Muscle Cells. J. Biol. Chem. 271: 16047-16052 [Abstract] [Full Text]  
• McKenzie, F. R., Pouyssegur, J. (1996). cAMP-mediated Growth Inhibition in Fibroblasts Is Not Mediated via Mitogen-activated Protein (MAP) Kinase (ERK) Inhibition. cAMP-DEPENDENT PROTEIN KINASE INDUCES A TEMPORAL SHIFT IN GROWTH FACTOR-STIMULATED MAP KINASES. J. Biol. Chem. 271: 13476-13483 [Abstract] [Full Text]  
• Blank, J. L., Gerwins, Pär, Elliott, E. M., Sather, S., Johnson, G. L. (1996). Molecular Cloning of Mitogen-activated Protein/ERK Kinase Kinases (MEKK) 2 and 3. J. Biol. Chem. 271: 5361-5368 [Abstract] [Full Text]  
• Shapiro, P. S., Evans, J. N., Davis, R. J., Posada, J. A. (1996). The Seven-transmembrane-spanning Receptors for Endothelin and Thrombin Cause Proliferation of Airway Smooth Muscle Cells and Activation of the Extracellular Regulated Kinase and c-Jun NH(2)-terminal Kinase Groups of Mitogen-activated Protein Kinases. J. Biol. Chem. 271: 5750-5754 [Abstract] [Full Text]  
• Okada, T., Masuda, T., Shinkai, M., Kariya, K.-i., Kataoka, T. (1996). Post-translational Modification of H-Ras Is Required for Activation of, but Not for Association with, B-Raf. J. Biol. Chem. 271: 4671-4678 [Abstract] [Full Text]  
• Wu, X., Noh, S. J., Zhou, G., Dixon, J. E., Guan, K.-L. (1996). Selective Activation of MEK1 but Not MEK2 by A-Raf from Epidermal Growth Factor-stimulated Hela Cells. J. Biol. Chem. 271: 3265-3271 [Abstract] [Full Text]  
• Knall, C., Young, S., Nick, J. A., Buhl, A. M., Worthen, G. S., Johnson, G. L. (1996). Interleukin-8 Regulation of the Ras/Raf/Mitogen-activated Protein Kinase Pathway in Human Neutrophils. J. Biol. Chem. 271: 2832-2838 [Abstract] [Full Text]  
• Ohtsuka, T., Shimizu, K., Yamamori, B., Kuroda, S., Takai, Y. (1996). Activation of Brain B-Raf Protein Kinase by Rap1B Small GTP-binding Protein. J. Biol. Chem. 271: 1258-1261 [Abstract] [Full Text]  
• 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]  
• Bogoyevitch, M. A., Marshall, C. J., Sugden, P. H. (1995). Hypertrophic Agonists Stimulate the Activities of the Protein Kinases c-Raf and A-Raf in Cultured Ventricular Myocytes. J. Biol. Chem. 270: 26303-26310 [Abstract] [Full Text]  
• Scott, A., Haystead, C. M. M., Haystead, T. A. J. (1995). Purification of a 12,020-Dalton Protein That Enhances the Activation of Mitogen-activated Protein (MAP) Kinase by MAP Kinase Kinase. J. Biol. Chem. 270: 24540-24547 [Abstract] [Full Text]  
• Barnier, J. V., Papin, C., Eychène, A., Lecoq, O., Calothy, G. (1995). The Mouse B-raf Gene Encodes Multiple Protein Isoforms with Tissue-specific Expression. J. Biol. Chem. 270: 23381-23389 [Abstract] [Full Text]  
• Ahmed, M. U., Hazeki, K., Hazeki, O., Katada, T., Ui, M. (1995). Cyclic AMP-increasing Agents Interfere with Chemoattractant-induced Respiratory Burst in Neutrophils as a Result of the Inhibition of Phosphatidylinositol 3-Kinase Rather than Receptor-operated Ca[IMAGE] Influx. J. Biol. Chem. 270: 23816-23822 [Abstract] [Full Text]  
• Withers, D. J., Bloom, S. R., Rozengurt, E. (1995). Dissociation of cAMP-stimulated Mitogenesis from Activation of the Mitogen-activated Protein Kinase Cascade in Swiss 3T3 Cells. J. Biol. Chem. 270: 21411-21419 [Abstract] [Full Text]  
• Hershenson, M. B., Chao, T.-S. O., Abe, M. K., Gomes, I., Kelleher, M. D., Solway, J., Rosner, M. R. (1995). Histamine Antagonizes Serotonin and Growth Factor-induced Mitogen-activated Protein Kinase Activation in Bovine Tracheal Smooth Muscle Cells. J. Biol. Chem. 270: 19908-19913 [Abstract] [Full Text]  
• Hsueh, Y.-P., Lai, M.-Z. (1995). c-Jun N-terminal Kinase but Not Mitogen-activated Protein Kinase Is Sensitive to cAMP Inhibition in T Lymphocytes. J. Biol. Chem. 270: 18094-18098 [Abstract] [Full Text]  
• Yamamori, B., Kuroda, S., Shimizu, K., Fukui, K., Ohtsuka, T., Takai, Y. (1995). Purification of a Ras-dependent Mitogen-activated Protein Kinase Kinase Kinase from Bovine Brain Cytosol and Its Identification as a Complex of B-Raf and 14-3-3 Proteins. J. Biol. Chem. 270: 11723-11726 [Abstract] [Full Text]  
• Frödin, M., Sekine, N., Roche, E., Filloux, C., Prentki, M., Wollheim, C. B., Van Obberghen, E. (1995). Glucose, Other Secretagogues, and Nerve Growth Factor Stimulate Mitogen-activated Protein Kinase in the Insulin-secreting beta-Cell Line, INS-1. J. Biol. Chem. 270: 7882-7889 [Abstract] [Full Text]  
• Reuter, C. W. M., Catling, A. D., Jelinek, T., Weber, M. J. (1995). Biochemical Analysis of MEK Activation in NIH3T3 Fibroblasts. J. Biol. Chem. 270: 7644-7655 [Abstract] [Full Text]  
• Fujita-Yoshigaki, J., Shirouzu, M., Ito, Y., Hattori, S., Furuyama, S., Nishimura, S., Yokoyama, S. (1995). A Constitutive Effector Region on the C-terminal Side of Switch I of the Ras Protein. J. Biol. Chem. 270: 4661-4667 [Abstract] [Full Text]  
• Booden, M. A., Sakaguchi, D. S., Buss, J. E. (2000). Mutation of Ha-Ras C Terminus Changes Effector Pathway Utilization. J. Biol. Chem. 275: 23559-23568 [Abstract] [Full Text]  
• Schmitt, J. M., Stork, P. J. S. (2000). beta 2-Adrenergic Receptor Activates Extracellular Signal-regulated Kinases (ERKs) via the Small G Protein Rap1 and the Serine/Threonine Kinase B-Raf. J. Biol. Chem. 275: 25342-25350 [Abstract] [Full Text]  
• Qiu, W., Zhuang, S., von Lintig, F. C., Boss, G. R., Pilz, R. B. (2000). Cell Type-specific Regulation of B-Raf Kinase by cAMP and 14-3-3 Proteins. J. Biol. Chem. 275: 31921-31929 [Abstract] [Full Text]  
• Guo, F.-f., Kumahara, E., Saffen, D. (2001). A CalDAG-GEFI/Rap1/B-Raf Cassette Couples M1 Muscarinic Acetylcholine Receptors to the Activation of ERK1/2. J. Biol. Chem. 276: 25568-25581 [Abstract] [Full Text]  
• Sidovar, M. F., Kozlowski, P., Lee, J. W., Collins, M. A., He, Y., Graves, L. M. (2000). Phosphorylation of Serine 43 Is Not Required for Inhibition of c-Raf Kinase by the cAMP-dependent Protein Kinase. J. Biol. Chem. 275: 28688-28694 [Abstract] [Full Text]