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The FASEB Journal, Vol 9, 1311-1318, Copyright © 1995 by The Federation of American Societies for Experimental Biology
REVIEWS |
MS Marshall
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
The 21 kDa Ras proteins are well known for their regulatory role in oncogenic, mitogenic, and developmental signaling pathways. Less well understood are the downstream signal transduction cascades initiated by Ras in response to external stimuli. Only recently have many diverse studies in lower eukaryotes and vertebrates converged to demonstrate that Ras directly regulates multiple signaling pathways. In most eukaryotes, Ras functions as a positive regulator of an ERK/MAPK signal transduction cascade through the activation of a MEKK. In mammalian cells the primary Ras-responsive MEKK is the protein kinase Raf. Although Raf remains the most significant mediator of Ras signaling in most model systems, it does not explain all the biochemical responses observed in cells with activated Ras proteins. Yeast two hybrid and GST- fusion protein binding studies have identified new proteins distinct from Raf that could interact with Ras in other signaling pathways. In addition to Raf, other potential Ras target proteins include MEKK1, PI(3)K, p120GAP, ralGDS, and PKC zeta. This review will attempt to summarize the current literature of accepted and potential Ras- dependent signaling proteins in both lower eukaryotes and vertebrates.
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L. Aubry, M. Maeda, R. Insall, P. N. Devreotes, and R. A. Firtel The Dictyostelium Mitogen-activated Protein Kinase ERK2 Is Regulated by Ras and cAMP-dependent Protein Kinase (PKA) and Mediates PKA Function J. Biol. Chem., February 14, 1997; 272(7): 3883 - 3886. [Abstract] [Full Text] [PDF] |
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J.-J. Yang and R. S. Krauss Extracellular ATP Induces Anchorage-independent Expression of Cyclin A and Rescues the Transformed Phenotype of a Ras-resistant Mutant Cell Line J. Biol. Chem., January 31, 1997; 272(5): 3103 - 3108. [Abstract] [Full Text] [PDF] |
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S Lee, R Escalante, and R. Firtel A Ras GAP is essential for cytokinesis and spatial patterning in Dictyostelium Development, January 3, 1997; 124(5): 983 - 996. [Abstract] [PDF] |
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S. A. Prigent, M. Nagane, H. Lin, I. Huvar, G. R. Boss, J. R. Feramisco, W. K. Cavenee, and H.-J. S. Huang Enhanced Tumorigenic Behavior of Glioblastoma Cells Expressing a Truncated Epidermal Growth Factor Receptor Is Mediated through the Ras-Shc-Grb2 Pathway J. Biol. Chem., October 11, 1996; 271(41): 25639 - 25645. [Abstract] [Full Text] [PDF] |
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J. Si, Z. Luo, and L. Mei Induction of Acetylcholine Receptor Gene Expression by ARIA Requires Activation of Mitogen-activated Protein Kinase J. Biol. Chem., August 16, 1996; 271(33): 19752 - 19759. [Abstract] [Full Text] [PDF] |
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T. Clementz, J. J. Bednarski, and C. R. H. Raetz Function of the htrB High Temperature Requirement Gene of Escherichia coli in the Acylation of Lipid A J. Biol. Chem., May 17, 1996; 271(20): 12095 - 12102. [Abstract] [Full Text] [PDF] |
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N. L. S. Que, S. Lin, R. J. Cotter, and C. R. H. Raetz Purification and Mass Spectrometry of Six Lipid A Species from the Bacterial Endosymbiont Rhizobium etli. DEMONSTRATION OF A CONSERVED DISTAL UNIT AND A VARIABLE PROXIMAL PORTION J. Biol. Chem., September 1, 2000; 275(36): 28006 - 28016. [Abstract] [Full Text] [PDF] |
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M. M. Kavurma, F. S. Santiago, E. Bonfoco, and L. M. Khachigian Sp1 Phosphorylation Regulates Apoptosis via Extracellular FasL-Fas Engagement J. Biol. Chem., February 9, 2001; 276(7): 4964 - 4971. [Abstract] [Full Text] [PDF] |
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M. G. Rudolph, T. Linnemann, P. Grunewald, A. Wittinghofer, I. R. Vetter, and C. Herrmann Thermodynamics of Ras/Effector and Cdc42/Effector Interactions Probed by Isothermal Titration Calorimetry J. Biol. Chem., June 22, 2001; 276(26): 23914 - 23921. [Abstract] [Full Text] [PDF] |
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