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Science 12 November 1993:
Vol. 262. no. 5136, pp. 1065 - 1069
DOI: 10.1126/science.7694366
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Articles

Science, Vol 262, Issue 5136, 1065-1069
Copyright © 1993 by American Association for the Advancement of Science

articles

Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate

J Wu, P Dent, T Jelinek, A Wolfman, MJ Weber, and TW Sturgill

Department of Internal Medicine, University of Virginia, Health Sciences Center, Charlottesville 22908.

Mitogen-activated protein (MAP) kinases p42mapk and p44mapk are activated in cells stimulated with epidermal growth factor (EGF) and other agents. A principal pathway for MAP kinase (MAPK) activation by EGF consists of sequential activations of the guanine nucleotide exchange factor Sos, the guanosine triphosphate binding protein Ras, and the protein kinases Raf-1, MAPK kinase (MKK), and MAPK. Because adenosine 3',5'-monophosphate (cAMP) does not activate MAPK and has some opposing physiologic effects, the effect of increasing intracellular concentrations of cAMP with forskolin and 3-isobutyl-1-methylxanthine on the EGF-stimulated MAPK pathway was studied. Increased concentrations of cAMP blocked activation of Raf-1, MKK, and MAPK in Rat1hER fibroblasts, accompanied by a threefold increase in Raf-1 phosphorylation on serine 43 in the regulatory domain. Phosphorylation of Raf-1 in vitro and in vivo reduces the apparent affinity with which it binds to Ras and may contribute to the blockade by cAMP.


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Mutagenesis 16, 17-23
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Adrenergic Regulation of Mitogen-Activated Protein Kinase in Rat Pinealocytes: Opposing Effects of Protein Kinase A and Protein Kinase G.
A. K. Ho and C. L. Chik (2000)
Endocrinology 141, 4496-4502
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CD28 and the Tyrosine Kinase Lck Stimulate Mitogen-Activated Protein Kinase Activity in T Cells via Inhibition of the Small G Protein Rap1.
K. D. Carey, T. J. Dillon, J. M. Schmitt, A. M. Baird, A. D. Holdorf, D. B. Straus, A. S. Shaw, and P. J. S. Stork (2000)
Mol. Cell. Biol. 20, 8409-8419
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p38MAPK Inhibition Enhances Basal and Norepinephrine-Stimulated p42/44MAPK Phosphorylation in Rat Pinealocytes.
M. Mackova, J. R. Man, C. L. Chik, and A. K. Ho (2000)
Endocrinology 141, 4202-4208
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Differential cAMP Gating of Glutamatergic Signaling Regulates Long-Term State Changes in the Suprachiasmatic Circadian Clock.
S. A. Tischkau, E. A. Gallman, G. F. Buchanan, and M. U. Gillette (2000)
J. Neurosci. 20, 7830-7837
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Cell-Type Specific Integration of Cross-Talk between Extracellular Signal-Regulated Kinase and cAMP Signaling.
M. D. Houslay and W. Kolch (2000)
Mol. Pharmacol. 58, 659-668
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Both Src-Dependent and -Independent Mechanisms Mediate Phosphatidylinositol 3-Kinase Regulation of Colony-Stimulating Factor 1-Activated Mitogen-Activated Protein Kinases in Myeloid Progenitors.
A. W.-M. Lee and D. J. States (2000)
Mol. Cell. Biol. 20, 6779-6798
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Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase.
N. Defer, M. Best-Belpomme, and J. Hanoune (2000)
Am J Physiol Renal Physiol 279, F400-F416
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Role of Ras-dependent ERK activation in phorbol ester-induced endothelial cell barrier dysfunction.
A. D. Verin, F. Liu, N. Bogatcheva, T. Borbiev, M. B. Hershenson, P. Wang, and J. G. N. Garcia (2000)
Am J Physiol Lung Cell Mol Physiol 279, L360-L370
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