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Science 2 September 1994:
Vol. 265. no. 5177, pp. 1458 - 1461
DOI: 10.1126/science.8073291
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Articles

Science, Vol 265, Issue 5177, 1458-1461
Copyright © 1994 by American Association for the Advancement of Science

articles

Ras-dependent growth factor regulation of MEK kinase in PC12 cells

CA Lange-Carter and GL Johnson

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

Mitogen-activated protein kinases (MAPKs) are rapidly activated in response to stimulation of diverse receptor types. MAPKs are positively regulated by phosphorylation on threonine and tyrosine by MAP kinase or extracellular signal-regulated kinase (ERK) kinases (MEKs). MEK kinase (MEKK) is part of a family of serine-threonine protein kinases that phosphorylate and activate MEKs independently of Raf. MEKK was rapidly and persistently activated in response to stimulation of resting PC12 cells with epidermal growth factor (EGF). Nerve growth factor (NGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) also activated MEKK, although to a lesser degree than did EGF. Activation of MEKK and B-Raf in response to EGF was inhibited by expression of dominant negative N17Ras. Expression of oncogenic Ras resulted in activation of MEKK. Stimulation of synthesis of cyclic adenosine 3',5'-monophosphate abolished activation of MEKK and B-Raf by EGF, NGF, and TPA. Thus, Ras simultaneously controls the activation of members of the Raf and MEKK families of protein kinases.


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H. Kamata, C. Tanaka, H. Yagisawa, S. Matsuda, Y. Gotoh, E. Nishida, and H. Hirata (1996)
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Y.-R. Chen, X. Wang, D. Templeton, R. J. Davis, and T.-H. Tan (1996)
J. Biol. Chem. 271, 31929-31936
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K. Carel, J. L. Kummer, C. Schubert, W. Leitner, K. A. Heidenreich, and B. Draznin (1996)
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J. Biol. Chem. 271, 20713-20718
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S. Kuroda, T. Ohtsuka, B. Yamamori, K. Fukui, K. Shimizu, and Y. Takai (1996)
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T. Ishizuka, A. Oshiba, N. Sakata, N. Terada, G. L. Johnson, and E. W. Gelfand (1996)
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J. Biol. Chem. 271, 6389-6397
   Abstract »    Full Text »    PDF »
Molecular Cloning of Mitogen-activated Protein/ERK Kinase Kinases (MEKK) 2 and 3.
J. L. Blank, Pär Gerwins, E. M. Elliott, S. Sather, and G. L. Johnson (1996)
J. Biol. Chem. 271, 5361-5368
   Abstract »    Full Text »    PDF »
Signal Transduction Pathways Regulated by Mitogen-activated/Extracellular Response Kinase Kinase Kinase Induce Cell Death.
N. L. Johnson, A. M. Gardner, K. M. Diener, C. A. Lange-Carter, J. Gleavy, M. B. Jarpe, A. Minden, M. Karin, L. I. Zon, and G. L. Johnson (1996)
J. Biol. Chem. 271, 3229-3237
   Abstract »    Full Text »    PDF »
Persistent Activation of c-Jun N-terminal Kinase 1 (JNK1) in [IMAGE] Radiation-induced Apoptosis.
Y.-R. Chen, C. F. Meyer, and T.-H. Tan (1996)
J. Biol. Chem. 271, 631-634
   Abstract »    Full Text »    PDF »
Rad, a Novel Ras-related GTPase, Interacts with Skeletal Muscle beta-Tropomyosin.
J. Zhu, P. J. Bilan, J. S. Moyers, D. A. Antonetti, and C. R. Kahn (1996)
J. Biol. Chem. 271, 768-773
   Abstract »    Full Text »    PDF »
Discordant Signal Transduction and Growth Inhibition of Small Cell Lung Carcinomas Induced by Expression of GTPase-deficient Galpha[IMAGE].
L. E. Heasley, J. Zamarripa, B. Storey, B. Helfrich, F. M. Mitchell, P. A. Bunn Jr., and G. L. Johnson (1996)
J. Biol. Chem. 271, 349-354
   Abstract »    Full Text »    PDF »
Ras Is Not Required for the Interleukin 3-induced Proliferation of a Mouse Pro-B Cell Line, BaF3.
K. Terada, Y. Kaziro, and T. Satoh (1995)
J. Biol. Chem. 270, 27880-27886
   Abstract »    Full Text »    PDF »
Hypertrophic Agonists Stimulate the Activities of the Protein Kinases c-Raf and A-Raf in Cultured Ventricular Myocytes.
M. A. Bogoyevitch, C. J. Marshall, and P. H. Sugden (1995)
J. Biol. Chem. 270, 26303-26310
   Abstract »    Full Text »    PDF »
The Farnesyl Group of H-Ras Facilitates the Activation of a Soluble Upstream Activator of Mitogen-activated Protein Kinase.
P. McGeady, S. Kuroda, K. Shimizu, Y. Takai, and M. H. Gelb (1995)
J. Biol. Chem. 270, 26347-26351
   Abstract »    Full Text »    PDF »
Molecular Cloning of a New Member of the p21-Cdc42/Rac-activated Kinase (PAK) Family.
E. Manser, C. Chong, Z.-S. Zhao, T. Leung, G. Michael, C. Hall, and L. Lim (1995)
J. Biol. Chem. 270, 25070-25078
   Abstract »    Full Text »    PDF »
The Mouse B-raf Gene Encodes Multiple Protein Isoforms with Tissue-specific Expression.
J. V. Barnier, C. Papin, A. Eychène, O. Lecoq, and G. Calothy (1995)
J. Biol. Chem. 270, 23381-23389
   Abstract »    Full Text »    PDF »
Increased Phosphorylation of Histone H1 in Mouse Fibroblasts Transformed with Oncogenes or Constitutively Active Mitogen-activated Protein Kinase Kinase.
D. N. Chadee, W. R. Taylor, R. A. R. Hurta, C. D. Allis, J. A. Wright, and J. R. Davie (1995)
J. Biol. Chem. 270, 20098-20105
   Abstract »    Full Text »    PDF »
Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes..
S A McCarthy, M L Samuels, C A Pritchard, J A Abraham, and M McMahon (1995)
Genes & Dev. 9, 1953-1964
   Abstract »    PDF »
The Regulation of AP-1 Activity by Mitogen-activated Protein Kinases.
M. Karin and M. Karin (1995)
J. Biol. Chem. 270, 16483-16486
   Full Text »    PDF »
How MAP Kinases Are Regulated.
M. H. Cobb and E. J. Goldsmith (1995)
J. Biol. Chem. 270, 14843-14846
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Activation of Protein Kinase Cascades by Osmotic Shock.
S. Matsuda, H. Kawasaki, T. Moriguchi, Y. Gotoh, and E. Nishida (1995)
J. Biol. Chem. 270, 12781-12786
   Abstract »    Full Text »    PDF »
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.
B. Yamamori, S. Kuroda, K. Shimizu, K. Fukui, T. Ohtsuka, and Y. Takai (1995)
J. Biol. Chem. 270, 11723-11726
   Abstract »    Full Text »    PDF »
Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1).
M. Russell, C. A. Lange-Carter, and G. L. Johnson (1995)
J. Biol. Chem. 270, 11757-11760
   Abstract »    Full Text »    PDF »
Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation..
K Galaktionov, C Jessus, and D Beach (1995)
Genes & Dev. 9, 1046-1058
   Abstract »    PDF »
Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2.
A Lin, A Minden, H Martinetto, F. Claret, C Lange-Carter, F Mercurio, G. Johnson, and M Karin (1995)
Science 268, 286-290
   Abstract »    PDF »
Glucose, Other Secretagogues, and Nerve Growth Factor Stimulate Mitogen-activated Protein Kinase in the Insulin-secreting beta-Cell Line, INS-1.
M. Frödin, N. Sekine, E. Roche, C. Filloux, M. Prentki, C. B. Wollheim, and E. Van Obberghen (1995)
J. Biol. Chem. 270, 7882-7889
   Abstract »    Full Text »    PDF »


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