Synonyms
List of Discussed GEFs
RapGEF1: C3G
RapGEF2: PDZ-GEF1, RA-GEF, CnRasGEF, KIAA0313, nRapGEP
RapGEF3: Epac, cAMP-GEF I
RapGEF4: Epac2, cAMP-GEF II
RapGEF5: MR-GEF, Repac, GFR, KIAA0277
RapGEF6: PDZ-GEF2, RA-GEF2
RasGRP2: CalDAG-GEF I
RasGRP3: GRP3, CalDAG-GEF III, KIAA0846
RasGEF1
SmgGDS: RAP1GDS1
Historical Background
GTP binding proteins are extensively used in nature to regulate biological processes. Most of these proteins act as molecular switches that transition between inactive GDP-bound and active GTP-bound conformations. The largest family of GDP/GTP switches is the Ras superfamily of small-molecular-weight GTP-binding proteins that constitute approximately 150 members in mammalian cells. This superfamily can be subdivided into Ras, Rho, Rab, Ran, and ARF families that regulate a myriad of cellular functions (Wennerberg et al. 2005). True Ras proteins play major roles in coupling cell surface receptors to intracellular signaling...
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Banerjee U, Cheng X. Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: structure, function and therapeutics. Gene. 2015;570(2):157–67.
Bithell A, Hsu T, Kandanearatchi A, Landau S, Everall IP, Tsuang MT, et al. Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder. PLoS One. 2010;5(4):e10392.
Borland G, Smith BO, Yarwood SJ. EPAC proteins transduce diverse cellular actions of cAMP. Br J Pharmacol. 2009;158(1):70–86.
Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov. 2014;13(11):828–51.
Gloerich M, Bos JL. Regulating Rap small G-proteins in time and space. Trends Cell Biol. 2011;21(10):615–23.
Hamel B, Monaghan-Benson E, Rojas RJ, Temple BR, Marston DJ, Burridge K, et al. SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC. J Biol Chem. 2011;286(14):12141–8.
Hobbs GA, Der CJ, Rossman KL. RAS isoforms and mutations in cancer at a glance. J Cell Sci. 2016;129(7):1287–92.
Hong KW, Jin HS, Lim JE, Ryu HJ, Go MJ, Lee JY, et al. RAPGEF1 gene variants associated with type 2 diabetes in the Korean population. Diabetes Res Clin Pract. 2009;84(2):117–22.
Li Y, Asuri S, Rebhun JF, Castro AF, Paranavitana NC, Quilliam LA. The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane. J Biol Chem. 2006;281(5):2506–14.
Maeta K, Edamatsu H, Nishihara K, Ikutomo J, Bilasy SE, Kataoka T. Crucial role of Rapgef2 and Rapgef6, a family of guanine nucleotide exchange factors for Rap1 small GTPase, in formation of apical surface adherens junctions and neural progenitor development in the mouse cerebral cortex. eNeuro. 2016;3(3):1–17.
Quilliam LA, Rebhun JF, Castro AF. A growing number of guanine nucleotide exchange factors is responsible for activation of ras family GTPases. Prog Nucleic Acid Res Mol Biol. 2002;71:391–444.
Sakurai A, Fukuhara S, Yamagishi A, Sako K, Kamioka Y, Masuda M, et al. MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin-mediated cell adhesion. Mol Biol Cell. 2006;17(2):966–76.
Satyanarayana A, Gudmundsson KO, Chen X, Coppola V, Tessarollo L, Keller JR, et al. RapGEF2 is essential for embryonic hematopoiesis but dispensable for adult hematopoiesis. Blood. 2010;116(16):2921–31.
Severson EA, Lee WY, Capaldo CT, Nusrat A, Parkos CA. Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell. 2009;20(7):1916–25.
Suh PG, Park JI, Manzoli L, Cocco L, Peak JC, Katan M, et al. Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep. 2008;41(6):415–34.
Wang H, Singh SR, Zheng Z, Oh SW, Chen X, Edwards K, et al. Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis. Dev Cell. 2006;10(1):117–26.
Wennerberg K, Rossman KL, Der CJ. The Ras superfamily at a glance. J Cell Sci. 2005;118(Pt 5):843–6.
Williams CL. A new signaling paradigm to control the prenylation and trafficking of small GTPases. Cell Cycle. 2013;12(18):2933–4.
Yaman E, Gasper R, Koerner C, Wittinghofer A, Tazebay UH. RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchange. FEBS J. 2009;276(16):4607–16.
Yoshikawa Y, Satoh T, Tamura T, Wei P, Bilasy SE, Edamatsu H, et al. The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-alpha dependent regulation of integrin activation in splenocytes. Mol Biol Cell. 2007;18(8):2949–59.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Quilliam, L.A. (2018). Rap GEF Family. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_274
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_274
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences