Rap (Protein)

Rap (von Ras-related protein ‚Ras-verwandtes Protein‘) ist eine Proteingruppe kleiner GTPasen aus der Ras-Superfamilie.

Eigenschaften

Rap-Proteine sind hochkonserviert in Schleimpilzen, Drosophila melanogaster und auch im Menschen und weisen ca. 50 % Homologie zur Aminosäuresequenz der Ras-Proteine auf. Wie alle Ras-verwandten Proteine spielen Rap-Proteine eine bedeutende Rolle in verschiedenen zellulären Regulationsprozessen wie Zelladhäsion, Zell-Zell-Kontakt, Zellformregulation und Zellmigration, Zellpolarität von Neuronen, synaptische Plastizität, Apoptosevermeidung sowie Hämatopoese.

Typen

Rap1 (in Drosophila auch „Roughened“, „Dras3“ oder CG1956): RAP1A, RAP1B
Rap2: RAP2A, RAP2B, RAP2C

Funktion

Wie jede GTPase benötigt auch Rap mindestens einen Guaninnukleotid-Austauschfaktor (GEF) sowie ein GTPase-aktivierendes Protein (GAP), um zwischen aktiver und inaktiver Form wechseln und seine Funktion ausüben zu können. Für Rap in Drosophila konnten bisher PDZ-GEF1 (auch „Dizzy“) als GEF und Rapgap1 als GAP identifiziert werden.

Weblinks

Commons: Rap – Sammlung von Bildern, Videos und Audiodateien

Einzelnachweise

↑ A. M. Rojas, G. Fuentes, A. Rausell, A. Valencia: The Ras protein superfamily: evolutionary tree and role of conserved amino acids. In: Journal of Cell Biology. Band 196, Nummer 2, Januar 2012, S. 189–201, doi:10.1083/jcb.201103008. PMID 22270915. PMC 3265948 (freier Volltext).
↑ K. Wennerberg, K. L. Rossman, C. J. Der: The Ras superfamily at a glance. In: Journal of cell science. Band 118, Pt 5, März 2005, S. 843–846, doi:10.1242/jcs.01660. PMID 15731001.
↑ SM Robbins, M Khosla, R Thiery, G Weeks, GB. Spiegelman: Ras-related genes in Dictyostelium discoideum. In: Dev Genet., 1991, 12(1-2), S. 147–153, PMID 2049874
↑ FS Neuman-Silberberg, E Schejter, FM Hoffmann, BZ. Shilo: The Drosophila ras oncogenes: structure and nucleotide sequence. In: Cell., 1984, 37,(3), S. 1027–1033, PMID 6430564
↑ IK Hariharan, RW Carthew, GM. Rubin: The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. In: Cell., 1991, 67(4), S. 717–722, PMID 1934069
↑ V Pizon, P Chardin, I Lerosey, B Olofsson, A. Tavitian: Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the ‘effector’ region. In: Oncogene., 1988, 3(2), S. 201–204, PMID 3045729
↑ AL Knox, NH. Brown: Rap1 GTPase Regulation of Adherens Junction Positioning and Cell Adhesion. In: Science, 295, 2002, S. 1285, PMID 11847339.
↑ C Hogan, N Serpente, P Cogram, CR Hosking, CU Bialucha, SM Feller, VM Braga, W Birchmeier, Y. Fujita: Rap1 Regulates the Formation of E-Cadherin-Based Cell-Cell Contacts. In: Mol. Cell Biol., 2004, 24(15), S. 6690, PMID 15254236
↑ LS Price, A Hajdo-Milasinovic, J Zhao, FJ Zwartkruis, JG Collard, JL. Bos: Rap1 regulates E-cadherin-mediated cell-cell adhesion. In: J. Biol. Chem., 2004, 279, S. 35127–35123, PMID 15166221
↑ WJ Pannekoek, MR Kooistra, FJ Zwartkruis, JL. Bos: Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors. (Review). In: Biochim. Biophys. Acta, 2009, 1788(4), S. 790–796, PMID 19159611
↑ H Kitayama, Y Sugimoto, T Matsuzaki, Y Ikawa, M. Noda: A ras-related gene with transformation suppressor activity. In: Cell., 1989, 56(1), S. 77–84, PMID 2642744
↑ H Asha, ND de Ruiter, MG Wang, IK. Hariharan: The Rap1 GTPase functions as a regulator of morphogenesis in vivo. In: EMBO J., 1999, 18(3), S. 605–615, PMID 9927420
↑ C. Spilker, M. R. Kreutz: RapGAPs in brain: multipurpose players in neuronal Rap signalling. In: The European journal of neuroscience. Band 32, Nummer 1, Juli 2010, S. 1–9, doi:10.1111/j.1460-9568.2010.07273.x, PMID 20576033.
↑ X. Ye, T. J. Carew: Small G protein signaling in neuronal plasticity and memory formation: the specific role of ras family proteins. In: Neuron. Band 68, Nummer 3, November 2010, S. 340–361, doi:10.1016/j.neuron.2010.09.013, PMC 3008420 (freier Volltext).
1 2 N. Minato: Rap G protein signal in normal and disordered lymphohematopoiesis. In: Experimental cell research. Band 319, Nummer 15, September 2013, S. 2323–2328, doi:10.1016/j.yexcr.2013.04.009, PMID 23603280.
↑ Rap1 auf Flybase. FlyBase-ID: FBgn0004636
↑ D. Vigil, J. Cherfils, K. L. Rossman, C. J. Der: Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? In: Nature Reviews Cancer. Band 10, Nummer 12, Dezember 2010, S. 842–857, doi:10.1038/nrc2960, PMC 3124093 (freier Volltext).
↑ I. M. Ahearn, K. Haigis, D. Bar-Sagi, M. R. Philips: Regulating the regulator: post-translational modification of RAS. In: Nature reviews. Molecular cell biology. Band 13, Nummer 1, Januar 2012, S. 39–51, doi:10.1038/nrm3255, PMC 3879958 (freier Volltext).
↑ M. Gloerich, J. L. Bos: Regulating Rap small G-proteins in time and space. In: Trends in cell biology. Band 21, Nummer 10, Oktober 2011, S. 615–623, doi:10.1016/j.tcb.2011.07.001, PMID 21820312.
↑ J de Rooij, NM Boenink, M van Triest, RH Cool, A Wittinghofer, JL. Bos: PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2. In: J Biol Chem., 1999, 274(53), S. 38125-38130, PMID 10608883
↑ F. Chen, M. Barkett, K. T. Ram, A. Quintanilla, I. K. Hariharan: Biological characterization of Drosophila Rapgap1, a GTPase activating protein for Rap1. In: Proc Natl Acad Sci U S A. Band 1997, Nr. 23, S. 12485–12490. PMID 9356476.

[1] A. M. Rojas, G. Fuentes, A. Rausell, A. Valencia: The Ras protein superfamily: evolutionary tree and role of conserved amino acids. In: Journal of Cell Biology. Band 196, Nummer 2, Januar 2012, S. 189–201, doi:10.1083/jcb.201103008. PMID 22270915. PMC 3265948 (freier Volltext).

[2] K. Wennerberg, K. L. Rossman, C. J. Der: The Ras superfamily at a glance. In: Journal of cell science. Band 118, Pt 5, März 2005, S. 843–846, doi:10.1242/jcs.01660. PMID 15731001.

[Robbins-3] SM Robbins, M Khosla, R Thiery, G Weeks, GB. Spiegelman: Ras-related genes in Dictyostelium discoideum. In: Dev Genet., 1991, 12(1-2), S. 147–153, PMID 2049874

[Neuman-Silberberg-4] FS Neuman-Silberberg, E Schejter, FM Hoffmann, BZ. Shilo: The Drosophila ras oncogenes: structure and nucleotide sequence. In: Cell., 1984, 37,(3), S. 1027–1033, PMID 6430564

[Hariharan-5] IK Hariharan, RW Carthew, GM. Rubin: The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. In: Cell., 1991, 67(4), S. 717–722, PMID 1934069

[Pizon-6] V Pizon, P Chardin, I Lerosey, B Olofsson, A. Tavitian: Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the ‘effector’ region. In: Oncogene., 1988, 3(2), S. 201–204, PMID 3045729

[Knox-7] AL Knox, NH. Brown: Rap1 GTPase Regulation of Adherens Junction Positioning and Cell Adhesion. In: Science, 295, 2002, S. 1285, PMID 11847339.

[Hogan-8] C Hogan, N Serpente, P Cogram, CR Hosking, CU Bialucha, SM Feller, VM Braga, W Birchmeier, Y. Fujita: Rap1 Regulates the Formation of E-Cadherin-Based Cell-Cell Contacts. In: Mol. Cell Biol., 2004, 24(15), S. 6690, PMID 15254236

[Price-9] LS Price, A Hajdo-Milasinovic, J Zhao, FJ Zwartkruis, JG Collard, JL. Bos: Rap1 regulates E-cadherin-mediated cell-cell adhesion. In: J. Biol. Chem., 2004, 279, S. 35127–35123, PMID 15166221

[Pannekoek-10] WJ Pannekoek, MR Kooistra, FJ Zwartkruis, JL. Bos: Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors. (Review). In: Biochim. Biophys. Acta, 2009, 1788(4), S. 790–796, PMID 19159611

[Kitayama-11] H Kitayama, Y Sugimoto, T Matsuzaki, Y Ikawa, M. Noda: A ras-related gene with transformation suppressor activity. In: Cell., 1989, 56(1), S. 77–84, PMID 2642744

[Asha-12] H Asha, ND de Ruiter, MG Wang, IK. Hariharan: The Rap1 GTPase functions as a regulator of morphogenesis in vivo. In: EMBO J., 1999, 18(3), S. 605–615, PMID 9927420

[13] C. Spilker, M. R. Kreutz: RapGAPs in brain: multipurpose players in neuronal Rap signalling. In: The European journal of neuroscience. Band 32, Nummer 1, Juli 2010, S. 1–9, doi:10.1111/j.1460-9568.2010.07273.x, PMID 20576033.

[14] X. Ye, T. J. Carew: Small G protein signaling in neuronal plasticity and memory formation: the specific role of ras family proteins. In: Neuron. Band 68, Nummer 3, November 2010, S. 340–361, doi:10.1016/j.neuron.2010.09.013, PMC 3008420 (freier Volltext).

[Minato-15] 1 2 N. Minato: Rap G protein signal in normal and disordered lymphohematopoiesis. In: Experimental cell research. Band 319, Nummer 15, September 2013, S. 2323–2328, doi:10.1016/j.yexcr.2013.04.009, PMID 23603280.

[Rap1_flybase-16] Rap1 auf Flybase. FlyBase-ID: FBgn0004636

[17] D. Vigil, J. Cherfils, K. L. Rossman, C. J. Der: Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? In: Nature Reviews Cancer. Band 10, Nummer 12, Dezember 2010, S. 842–857, doi:10.1038/nrc2960, PMC 3124093 (freier Volltext).

[18] I. M. Ahearn, K. Haigis, D. Bar-Sagi, M. R. Philips: Regulating the regulator: post-translational modification of RAS. In: Nature reviews. Molecular cell biology. Band 13, Nummer 1, Januar 2012, S. 39–51, doi:10.1038/nrm3255, PMC 3879958 (freier Volltext).

[19] M. Gloerich, J. L. Bos: Regulating Rap small G-proteins in time and space. In: Trends in cell biology. Band 21, Nummer 10, Oktober 2011, S. 615–623, doi:10.1016/j.tcb.2011.07.001, PMID 21820312.

[deRooij-20] J de Rooij, NM Boenink, M van Triest, RH Cool, A Wittinghofer, JL. Bos: PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2. In: J Biol Chem., 1999, 274(53), S. 38125-38130, PMID 10608883

[Chen-21] F. Chen, M. Barkett, K. T. Ram, A. Quintanilla, I. K. Hariharan: Biological characterization of Drosophila Rapgap1, a GTPase activating protein for Rap1. In: Proc Natl Acad Sci U S A. Band 1997, Nr. 23, S. 12485–12490. PMID 9356476.