The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Rac2 Regulates Neutrophil Chemotaxis, Superoxide Production, and Myeloid Colony Formation through Multiple Distinct Effector Pathways
Abstract
Polymorphonuclear neutrophils (PMN) are an important component of the innate immune system. We have shown previously that migration and superoxide (O⨪2) production, as well as some kinase signaling pathways are compromised in mice deficient in the Ras-related Rho GTPase Rac2. In this study, we demonstrate that Rac2 controls chemotaxis and superoxide production via distinct pathways and is critical for development of myeloid colonies in vitro. The Rac2 mutants V36A, F37A, and N39A all bind to both Pak1 and p67phox, yet are unable to rescue superoxide production and chemotaxis when expressed in Rac2−/− PMN. In contrast, the N43A mutant, which binds to Por1 (Arfaptin 2), p67phox, and Pak1, is able to rescue superoxide production but not chemotaxis. The F37A mutant, demonstrated to have reduced binding to Por1, shows reduced rescue of fMLP-induced chemotaxis. Finally, the Rac2Y40C mutant that is defective in binding to all three potential downstream effectors (Pak1, p67phox, and Por1) is unable to rescue chemotaxis, motility, or superoxide production, but is able to rescue defective growth of myeloid colonies in vitro. These findings suggest that binding to any single effector is not sufficient to rescue the distinct cellular phenotypes of Rac2−/− PMN, implicating multiple, distinct, and potentially parallel effector pathways.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Rac2 has been identified as a component of the phagocytic oxidase complex in neutrophils (Figure 1A)”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [22]
In the citing paper
“its deficiency results in impairment of both neutrophil chemotaxis in response to Formylmethionyl-Leucyl-Phenylalanine (fMLP) and superoxide production”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [22]
In the citing paper
“and is therefore associated with phagocyte immunodeficiency in humans17,18,19,20,21,22,23.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [22]
In the citing paper
“Generation of a Rac2-deficient mouse line helped to determine the broader hematopoietic phenotype and revealed the presence of a phagocytic immunodeficiency that was specifically associated with lack of Rac222,23,59.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [22]
In the citing paper
“Studies in mouse Rac2 2/2 neutrophils have demonstrated different effector proteins involved in O 2 • 2 production (p67 phox ) and cell migration (Pak1), indicating that multiple pathways are affected by the loss of Rac2 in these cells.26,33,34”
From Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects (2019) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Structure of the TPR Domain of p67phox in Complex with Rac·GTP
Lapouge, K., Smith, S. J. M., Walker, P. A., Gamblin, S. J., Smerdon, S. J., & Rittinger, K. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00091-2 · Cited by 311
Characterization of the Effector-specifying Domain of Rac Involved in NADPH Oxidase Activation
Kwong, C. H., Adams, A. G., & Leto, T. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.34.19868 · Cited by 76
Research works printed but not linked: 41
- 1999, Immunity, 183
- 2001, J. Biol. Chem., 15929
- 2001, J. Immunol., 1223
- 2002, Mol. Cell. Biol., 7645
- 2003, Science, 445
- 2002, Nature, 629
- 1998, J. Biol. Chem., 20685
- 2004, Nat. Immunol., 744
- 1996, Cell, 371
- 1999, Nat. Cell Biol., 253
- 1996, EMBO J., 3778
- 1999, Science, 2083
- 1999, Nat. Cell Biol., 242
- 2003, Nat. Cell Biol., 236
- 1996, Cell, 519
- 1996, Science, 810
- 1997, Mol. Cell Biol., 1324
- 1998, EMBO J., 1350
- 1995, J. Biol. Chem., 29071
- 2002, Nature, 442
- 2002, Blood, 2692
- 1994, Science, 531
- 1994, J. Biol. Chem., 23569
- 1995, J. Biol. Chem., 19868
- 1996, J. Biol. Chem., 19794
- 1997, J. Biol. Chem., 18834
- 1998, Oncogene, 625
- 2000, Blood, 1646
- 2000, Immunity, 557
- 1996, Nat. Med., 876
- 2002, Blood, 1679
- 2002, J. Immunol., 5043
- 1999, J. Immunol. Methods, 3
- 2003, Curr. Opin. Hematol., 8
- 2001, Nature, 215
- 2001, Nat. Cell Biol., 950
- 1998, J. Biol. Chem., 21512
- 1995, Science, 1270
- 1995, EMBO J., 5297
- 2000, Mol. Cell, 899
- 1996, Science, 1374
Cited by
Local force and geometry sensing regulate cell functions
Vogel, V., & Sheetz, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1890 · Cited by 2,328
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
Graham, D. B., Robertson, C. M., Bautista, J., Mascarenhas, F., Diacovo, M. J., Montgrain, V., Lam, S. K., Cremasco, V., Dunne, W. M., Faccio, R., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32729 · Cited by 124
Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects
Hsu, A. P., Donkó, A., Arrington, M. E., Swamydas, M., Fink, D., Das, A., Escobedo, O., Bonagura, V., Szabolcs, P., Steinberg, H. N., et al. (2019) · Blood · doi:10.1182/blood-2018-11-886028 · Cited by 92
Pai, S.-Y., Kim, C., & Williams, D. A. (2010) · Disease Markers · doi:10.1155/2010/380291 · Cited by 85
Self-citationIsozyme-specific stimulation of phospholipase C-γ2 by Rac GTPases
Piechulek, T., Rehlen, T., Walliser, C., Vatter, P., Moepps, B., & Gierschik, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509396200 · Cited by 80
Hematopoietic-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-citation
Metadata
- Authors
- Carstanjen, D., Yamauchi, A., Koornneef, A., Zang, H., Filippi, M.-D., Harris, C., Towe, J., Atkinson, S., Zheng, Y., Dinauer, M. C., & Williams, D. A.
- Affiliations
- Division of Experimental Hematology, Children’s Hospital Research Foundation , Cincinnati, OH
- Herman B Wells Center for Pediatric Research, Department of Pediatrics, Department, of Medicine, Indiana University School of Medicine , Indianapolis, IN
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-04
- Volume
- 174
- Issue
- 8
- Pages
- 4613-4620
- ISSN
- 0022-1767
- 1550-6606
- Cited by
- 56
- References
- 2
- Language
- en
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
