Historical Background
The Ras guanine nucleotide releasing factor (RasGrf) proteins were isolated in an effort to find mammalian homolog(s) of the yeast CDC25 Ras activator protein. The search for mammalian Ras GEFs during the early 1990s led to the discovery and isolation of the Son of sevenless (Sos) and the RasGrf proteins. Whereas the Sos proteins had ubiquitous expression, RasGrf expression was restricted mainly to the central nervous system. Soon after the discovery of the first member of the RasGrf family (RasGrf1) in neural tissues, a second highly homologous member of this family was isolated from embryonic stem cells (RasGrf2). Later on, a number of distinct, alternatively spliced isoforms have been described for both genes in a variety of tissues or developmental stages. RasGrf1 and RasGrf2 are large, modular proteins composed by multiple functional domains accounting for protein–protein or protein–lipid interactions which are...
This is a preview of subscription content, log in via an institution.
References
Arozarena I, Matallanas D, Crespo P. Maintenance of CDC42 GDP-bound state by Rho-GDI inhibits MAP kinase activation by the exchange factor Ras-GRF. evidence for Ras-GRF function being inhibited by Cdc42-GDP but unaffected by CDC42-GTP. J Biol Chem. 2001;276(24):21878–84.
Brambilla R, Gnesutta N, Minichiello L, White G, Roylance AJ, Herron CE, et al. A role for the Ras signaling pathway in synaptic transmission and long-term memory. Nature. 1997;390:281–6.
de Hoog CL, Fan W-T, Goldstein MD, Moran MF, Koch CA. Calmodulin-independent coordination of Ras and extracellular signal-regulated kinase activation by Ras-GRF2. Mol Cell Biol. 2000;20:2727–33.
Fernandez-Medarde A, Barhoum R, Riquelme R, Porteros A, Nunez A, de Luis A, et al. RasGRF1 disruption causes retinal photoreception defects and associated transcriptomic alterations. J Neurochem. 2009;110(2):641–52.
Font de Mora J, Esteban LM, Burks DJ, Nunez A, Garces C, Garcia-Barrado MJ, et al. Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J. 2003;22(12):3039–49.
Freshney NW, Goonesekera SD, Feig LA. Activation of the exchange factor Ras-GRF by calcium requires an intact Dbl homology domain. FEBS Lett. 1997;407:111–5.
Innocenti M, Zippel R, Brambilla R, Sturani E. CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. FEBS Lett. 1999;460(2):357–62.
Kesavapany S, Pareek TK, Zheng YL, Amin N, Gutkind JS, Ma W, et al. Neuronal nuclear organization is controlled by cyclin-dependent kinase 5 phosphorylation of Ras guanine nucleotide releasing factor-1. Neurosignals. 2006;15(4):157–73.
Kiyono M, Kaziro Y, Satoh T. Induction of rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) following phosphorylation by the nonreceptor tyrosine kinase Src. J Biol Chem. 2000;275(8):5441–6.
Krapivinsky G, Krapivinsky L, Manasian Y, Ivanov A, Tyzio R, Pellegrino C, et al. The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron. 2003;40(4):775–84.
Li S, Tian X, Hartley DM, Feig LA. Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression. J Neurosci. 2006;26(6):1721–9.
Mattingly RR. Phosphorylation of serine 916 of Ras-GRF1 contributes to the activation of exchange factor activity by muscarinic receptors. J Biol Chem. 1999;274:37379–84.
Norum JH, Dawood H, Mattingly RR, Sandnes D, Levy FO. Epac- and Rap- independent ERK1/2 phosphorylation induced by Gs-coupled receptor stimulation in HEK293 cells. FEBS Lett. 2007;581(1):15–20.
Robinson KN, Manto K, Buchsbaum RJ, MacDonald JI, Meakin SO. Neurotrophin-dependent tyrosine phosphorylation of Ras guanine-releasing factor 1 and associated neurite outgrowth is dependent on the HIKE domain of TrkA. J Biol Chem. 2005;280(1):225–35.
Ruiz S, Santos E, Bustelo XR. RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses. Mol Cell Biol. 2007;27(23):8127–42.
Santos E, Fernandez-Medarde A. RasGrf1. UCSD-nature molecule pages. 2009. doi:10.1038/mp.a002032.01.
Santos E, Fernández-Medarde A. RasGrf2. UCSD-nature molecule pages. 2008. doi:10.1038/mp.a002441.01.
Tonini R, Ciardo S, Cerovic M, Rubino T, Parolaro D, Mazzanti M, et al. ERK-dependent modulation of cerebellar synaptic plasticity after chronic Delta9-tetrahydrocannabinol exposure. J Neurosci. 2006;26(21):5810–8.
Yoon B, Herman H, Hu B, Park YJ, Lindroth A, Bell A, et al. Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker. Mol Cell Biol. 2005;25(24):11184–90.
Zippel R, Orecchia S, Sturani E, Martegani E. The brain specific Ras exchange factor CDC25 Mm: modulation of its activity through Gi-protein-mediated signals. Oncogene. 1996;12(12):2697–703.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this entry
Cite this entry
Santos, E., Fernández-Medarde, A. (2012). RasGrf (RAS Protein-Specific Guanine Nucleotide-Releasing Factor). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_138
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0461-4_138
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0460-7
Online ISBN: 978-1-4419-0461-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences