The DOI matches its Crossref record.
Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils
Abstract
Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Subcellular localization of Rac proteins has been shown to be critical for signal transduction and cellular functions in other cells.13,19”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Diversity in the polybasic domains appears to confer the unique function and localization of the Rho GTPases.19”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Both RhoH (Figure 6A) and Rac1 have a conserved polybasic domain and a CAAX prenylation site in their C termini.7,19,30”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Rac1 and Rac2 also regulate distinct aspects of cytoskeletal reorganization (Filippi et al., 2004).”
From Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease (2007) · cites this paper as Filippi et al., 2004
In the citing paper
“Murine knock-out models have showed that despite the very high amino acid sequence homology, RAC1 and RAC2 have non-redundant functions in hematopoietic cells, which could be explained at least in part by the differences in the C-termini of the two proteins leading to their distinct subcellular distribution in murine neutrophils [47].”
From Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2 (2015) · cites this paper as [47]
1 more claim about this paper
Create a free account to see every claim other papers make about this one.
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 37
- Lim, L., Manser, E., Leung, T. & Hall, C. Regulation of phosphorylation pathways by p21 GTPases. The p21 Ras-related Rho subfamily and its role in phosphorylation signalling pathways. Eur. J. Biochem. 242, 171–185 (1996). · DOI
- Van Aelst, L. & D'Souza-Schorey, C. Rho GTPases and signaling networks. Genes Dev. 11, 2295–2322 (1997). · DOI
- Hall, A. G proteins and small GTPases: distant relatives keep in touch. Science 280, 2074–2075 (1998). · DOI
- Didsbury, J., Weber, R.F., Bokosh, G.M., Evans, T. & Synderman, R. Rac, a novel ras-related family of proteins that are botulinum toxin substrates. J. Biol. Chem. 264, 16378–16382 (1989). · DOI · Paper page
- Moll, J., Sansig, G., Fattori, E. & van der Putten, H. The murine rac1 gene: cDNA cloning, tissue distribution and regulated expression of rac1 mRNA by disassembly of actin microfilaments. Oncogene 6, 863–866 (1991).
- Shirsat, N.V., Pignolo, R.J., Kreider, B.L. & Rovera, G. A member of the ras gene superfamily is expressed specifically in T, B and myeloid hemopoietic cells. Oncogene 5, 769–772 (1990).
- Haataja, L., Groffen, J. & Heisterkamp, N. Characterization of RAC3, a novel member of the Rho family. J. Biol. Chem. 272, 20384–20388 (1997). · DOI · Paper page
- Gu, Y. et al. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302, 445–449 (2003). · DOI · Paper page
- Glogauer, M. et al. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions. J. Immunol. 170, 5652–5657 (2003). · DOI
- Li, S. et al. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. J. Immunol. 169, 5043–5051 (2002). · DOI · Paper page
- Roberts, A.W. et al. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 10, 183–196. (1999). · DOI · Paper page
- Williams, D.A. et al. Dominant negative mutation of the hematopoietic-specific RhoGTPase, Rac 2, is associated with a human phagocyte immunodeficiency. Blood 96, 1646–1654 (2000).
- Ambruso, D.R. et al. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc. Natl. Acad. Sci. USA 97, 4654–4659 (2000). · DOI · Paper page
- Diekmann, D., Nobes, C.D., Burbelo, P.D., Abo, A. & Hall, A. Rac GTPase interacts with GAPs and target proteins through multiple effector sites. EMBO J. 14, 5297–5305 (1995). · DOI · Paper page
- Zhang, F.L. & Casey, P.J. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241–269 (1996). · DOI · Paper page
- Gelb, M.H., Scholten, J.D. & Sebolt-Leopold, J.S. Protein prenylation: from discovery to prospects for cancer treatment. Curr. Opin. Chem. Biol. 2, 40–48 (1998). · DOI
- Tao, W. et al. The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization. Blood 100, 1679–1688 (2002). · DOI
- Michaelson, D. et al. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J. Cell. Biol. 152, 111–126 (2001). · DOI · Paper page
- Benard, V., Bohl, B.P. & Bokoch, G.M. Characterization of Rac and Cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J. Biol. Chem. 274, 13198–13204 (1999). · DOI · Paper page
- Joseph, G., Gorzalczany, Y., Koshkin, V. & Pick, E. Inhibition of NADPH oxidase activation by synthetic peptides mapping within the carboxyl-terminal domain of small GTP-binding proteins. Lack of amino acid sequence specificity and importance of polybasic motif. J. Biol. Chem. 269, 29024–29031 (1994). · DOI
- Gardiner, E.M. et al. Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr. Biol. 12, 2029–2034 (2002). · DOI
- Li, J.M. & Shah, A.M. Intracellular localization and preassembly of the NADPH oxidase complex in cultured endothelial cells. J. Biol. Chem. 277, 19952–19960 (2002). · DOI
- Scheffzek, K., Stephan, I., Jensen, O.N., Illenberger, D. & Gierschik, P. The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI. Nat. Struct. Biol. 7, 122–126 (2000). · DOI
- Grizot, S. et al. Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation. Biochemistry 40, 1000–10013 (2001).
- Dib, K. et al. Down-regulation of Rac activity during β2 integrin-mediated adhesion of human neutrophils. J. Biol. Chem. 278, 24181–24188 (2003). · DOI
- Hoffman, G.R., Nassar, N. & Cerione, R.A. Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100, 345–356 (2000). · DOI
- Roy, M.O., Leventis, R. & Silvius, J.R. Mutational and biochemical analysis of plasma membrane targeting mediated by the farnesylated, polybasic carboxy terminus of K-ras4B. Biochemistry 39, 8298–8307 (2000). · DOI
- Apolloni, A., Prior, I.A., Lindsay, M., Parton, R.G. & Hancock, J.F. H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Mol. Cell. Biol. 20, 2475–2487 (2000). · DOI
- Dong, X. et al. Palmitoylation and plasma membrane localization of Ras2p by a nonclassical trafficking pathway in Saccharomyces cerevisiae. Mol. Cell. Biol. 23, 6574–6584 (2003). · DOI
- Knaus, U.G., Wang, Y., Reilly, A.M., Warnock, D. & Jackson, J.H. Structural requirements for PAK activation by Rac GTPases. J. Biol. Chem. 273, 21512–21518 (1998). · DOI · Paper page
- Van Hennik, P.B. et al. The C-terminal domain of Rac1 contains two motifs that control targeting and signaling specificity. J. Biol. Chem. 278, 39166–39175 (2003). · DOI · Paper page
- Servant, G. et al. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287, 1037–1940. (2000). · DOI
- Weiner, O.D. et al. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nat. Cell. Biol. 4, 509–513 (2002). · DOI
- Wang, F. et al. Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat. Cell. Biol. 4, 513–518 (2002). · DOI
- Srinivasan, S. et al. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J. Cell. Biol. 160, 375–385 (2003). · DOI
- Yang, F.C. et al. Rac 2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin-based cell functions in primary mast cells. Immunity 12, 557–568 (2000). · DOI · Paper page
- Jackson, J.H. et al. Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. Proc. Natl. Acad. Sci. USA 87, 3042–3046 (1990). · DOI
Cited by
Neutrophils to the ROScue: Mechanisms of NADPH oxidase activation and bacterial resistance
Nguyen, G. T., Green, E. R., & Mecsas, J. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00373 · Cited by 741
Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization
Cancelas, J. A., Lee, A. W., Prabhakar, R., Stringer, K. F., Zheng, Y., & Williams, D. A. (2005) · Nature Medicine · doi:10.1038/nm1274 · Cited by 278
Self-citationArana, E., Vehlow, A., Harwood, N. E., Vigorito, E., Henderson, R., Turner, M., Tybulewicz, V. L. J., & Batista, F. D. (2008) · Immunity · doi:10.1016/j.immuni.2007.12.003 · Cited by 156
Thomas, E. K., Cancelas, J. A., Chae, H.-D., Cox, A. D., Keller, P. J., Perrotti, D., Neviani, P., Druker, B. J., Setchell, K. D. R., Zheng, Y., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.10.015 · Cited by 147
Self-citationROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation
Stojkov, D., Amini, P., Oberson, K., Sokollik, C., Duppenthaler, A., Simon, H.-U., & Yousefi, S. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201611168 · Cited by 142
Gu, Y., Chae, H.-D., Siefring, J. E., Jasti, A. C., Hildeman, D. A., & Williams, D. A. (2006) · Nature Immunology · doi:10.1038/ni1396 · Cited by 110
Self-citationPai, S.-Y., Kim, C., & Williams, D. A. (2010) · Disease Markers · doi:10.1155/2010/380291 · Cited by 85
Self-citationChae, H.-D., Lee, K. E., Williams, D. A., & Gu, Y. (2008) · Blood · doi:10.1182/blood-2007-06-093237 · Cited by 81
Self-citationHematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders
Troeger, A., & Williams, D. A. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.07.002 · Cited by 73
Self-citationUeyama, T., Eto, M., Kami, K., Tatsuno, T., Kobayashi, T., Shirai, Y., Lennartz, M. R., Takeya, R., Sumimoto, H., & Saito, N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.4.2381 · Cited by 50
Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2
Capala, M. E., Maat, H., Bonardi, F., van den Boom, V., Kuipers, J., Vellenga, E., Giepmans, B. N. G., & Schuringa, J. J. (2015) · PLOS ONE · doi:10.1371/journal.pone.0128585 · Cited by 20
RhoH/TTF Negatively Regulates Leukotriene Production in Neutrophils
Daryadel, A., Yousefi, S., Troi, D., Schmid, I., Schmidt-Mende, J., Mordasini, C., Dahinden, C. A., Ziemiecki, A., & Simon, H.-U. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803846 · Cited by 20
Metadata
- Authors
- Filippi, M.-D., Harris, C. E., Meller, J., Gu, Y., Zheng, Y., & Williams, D. A.
- Venue
- Nature Immunology
- Published
- 2004-05-30
- Volume
- 5
- Issue
- 7
- Pages
- 744-751
- ISSN
- 1529-2908
- 1529-2916
- Cited by
- 110
- References
- 0
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review