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Cited by 100Immunodeficiency and Autoimmune DisordersProtein Kinase Regulation and GTPase SignalingNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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Biochemical and Biological Characterization of a Human Rac2 GTPase Mutant Associated with Phagocytic Immunodeficiency

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Gu, Yi, Jia, Baoqing, Yang, Feng-Chun, D'Souza, Maria, Harris, Chad E., Derrow, Caroline W., Zheng, Yi, Williams, David A.·2001·Journal of Biological Chemistry
DOI 10.1074/jbc.m010445200
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Abstract

The Rho GTPase, Rac2, is expressed only in hematopoietic cell lineages, suggesting a specific cellular function in these cells. Genetic targeting studies in mice showed that Rac2 is an essential regulator of neutrophil chemotaxis, L-selectin capture and rolling, and superoxide production. Recently, a dominant negative mutation of Rac2, D57N, has been reported to be associated with a human phagocytic immunodeficiency. To understand further the cellular phenotypes associated with this D57N Rac2 mutant we examined its biochemical characteristics and functional effects when expressed in primary murine bone marrow cells. When compared with wild type (WT) Rac2, D57N Rac2 displayed approximately 10% GTP binding ability resulting from a markedly enhanced rate of GTP dissociation and did not respond to the guanine nucleotide exchange factors. These results suggest that D57N Rac2 may act in a dominant negative fashion in cells by sequestering endogenous guanine nucleotide exchange factors. When expressed in hematopoietic cells, D57N Rac2 reduced endogenous activities of not only Rac2, but also Rac1 and decreased cell expansion in vitro in the presence of growth factors due to increased cell apoptosis. Unexpectedly, D57N expression had no effect on proliferation. In contrast, expansion of cells transduced with WT Rac2 and a dominant active mutant, Q61L, was associated with significantly increased proliferation. Transplantation of transduced bone marrow cells into lethally irradiated recipients showed that the percentage of D57N-containing peripheral blood cells decreased markedly from 40% at 1 month to <5% by 3 months postinjection. Neutrophils derived in vitro from the transduced progenitor cells containing D57N demonstrated markedly impaired migration and O(2)(-) responses to formyl-methionyl-leucyl-phenylalanine, reflecting the same cellular phenotype in these differentiated cells as those described previously in patient cells. These data suggest that the phenotypic abnormalities associated with D57N Rac2 may involve not only neutrophil cellular functions, but also abnormal cell survival in other hematopoietic cells and that overexpression of Rac leads to increased proliferation of normal cells in vitro, whereas deficiency of Rac leads to increased apoptosis.

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TL;DR

The human Rac2 D57N mutant associated with phagocytic immunodeficiency has severely impaired GTP binding and rapid GTP dissociation, does not respond to GEF TrioN despite binding it, and acts dominantly to reduce Rac1 and Rac2 activity in hematopoietic cells. In primary murine bone marrow cells, D57N Rac2 impairs expansion and engraftment mainly by increasing apoptosis, while WT Rac2 or Q61L increases proliferation.

Key findings

  • D57N Rac2 bound GTP at only ~10% of normal, with rapid GTP dissociation reaching ~75% in 2 min, whereas WT Rac2 dissociated ~30% of GDP or GTP in 15 min; GDP dissociation was similar to WT.
  • D57N Rac2 did not respond to the Rac GEF TrioN, although GST-TrioN coprecipitated equally with WT and D57N Rac2; WT Rac2 exchanged ~90% to GTP-bound in 15 min with TrioN.
  • In transduced bone marrow cells, D57N Rac2 eliminated detectable GTP-bound Rac2 and also prevented GTP binding to endogenous Rac1; D57N completely inhibited chemotaxis and abolished superoxide production in differentiated myeloid cells.
  • D57N expression reduced cell expansion in vitro and long-term engraftment in vivo (peripheral blood D57N GFP+ cells fell from >25% to <10% at 1 month and <5% by 3 months in Results; abstract reports 40% at 1 month), associated with increased apoptosis (up to 90% annexin V+ at 13 days; TUNEL 14.8% vs 6.0% for MIEG3, p = 0.003) but no effect on DNA synthesis. WT Rac2 or Q61L increased proliferation (~4-fold in WT cells; 10-fold in Rac2−/− cells) and slightly reduced apoptosis.

Methods

  • Recombinant human WT and D57N Rac2 proteins were expressed in E. coli and used for guanine nucleotide binding/dissociation assays and GST-TrioN exchange-factor binding assays.
  • WT, D57N, and Q61L Rac2 cDNAs were introduced via MIEG3 retroviral vectors into murine low-density bone marrow cells from WT and Rac2−/− mice; GFP+ cells were analyzed by Western blot, PAK1 PBD pull-down, growth/colony assays, thymidine incorporation, annexin V/PI/TUNEL, chemotaxis, and NBT superoxide assays.
  • Transduced bone marrow cells were transplanted into lethally irradiated mice, and peripheral blood GFP+ cells were monitored monthly for engraftment.

Limitations

  • The paper states that the role of Rac2 in pluripotent hematopoietic stem/progenitor cells and other lineages remains unclear, the basis of Rac2 functional specificity is unknown, and the D57N phenotype in humans requires more careful future analysis.
  • The text notes that some results are “data not shown,” and Q61L transduction consistently gave only low gene transfer, limiting direct comparisons.
  • Evident from the text: in vitro culture of Rac2−/− cells upregulated Rac1 activity >5-fold and partially rescued migration/superoxide phenotypes, so cultured-cell results may not fully reflect in vivo Rac2 function.

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Crossref · 10.1074/jbc.m010445200

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Figures

FIG. 1 Intrinsic GTP/GDP dissociation of D57N Rac2 mutant. Recombinant WT Rac2 ( solid symbols ) and D57N Rac2 ( open symbols ) proteins were preloaded with either [ g -35 S]GTP ( circles ) or [ 3 H]GDP ( triangles ). Guanine nucleotide dissociation was initiated by adding the radionucleotide-loaded proteins to the activation buffer, and the remaining bound radioactivity was examined at different time points: 0, 2, 5, 10, and 15 min. The amount of bound nucleotide at t 5 0 min was set to 100%. The data are presented as the percentage of bound [ g -35 S]GTP or [ 3 H]GDP remaining. The results shown are representative of three experiments.
FIG. 1 Intrinsic GTP/GDP dissociation of D57N Rac2 mutant. Recombinant WT Rac2 ( solid symbols ) and D57N Rac2 ( open symbols ) proteins were preloaded with either [ g -35 S]GTP ( circles ) or [ 3 H]GDP ( triangles ). Guanine nucleotide dissociation was initiated by adding the radionucleotide-loaded proteins to the activation buffer, and the remaining bound radioactivity was examined at different time points: 0, 2, 5, 10, and 15 min. The amount of bound nucleotide at t 5 0 min was set to 100%. The data are presented as the percentage of bound [ g -35 S]GTP or [ 3 H]GDP remaining. The results shown are representative of three experiments.CC-BY · From the PDF
FIG. 2 GDP/GTPexchangeofD57NRac2mutantstimulated by guanine nucleotide exchange factor TrioN. Panel A , 2 m g of recombinant WT Rac2 ( circles ) and D57N Rac2 ( triangles ) were preloaded with [ 3 H]GDP and exchanged for cold GTP in the absence ( solid symbols ) or presence ( open symbols ) of 0.5 m g of TrioN. The remaining bound [ 3 H]GDP was determined at 0, 2, 5, 10, and 15 min after GTP exchange. The amount of bound nucleotide at t 5 0 min was set to 100%. The data are presented as the percentage of bound [ 3 H]GDP remaining. The results shown are representative of three experiments. Panel B , binding of guanine nucleotide exchange factor, TrioN, to WT and D57N Rac2. Purified recombinant His-tagged WT Rac2 and D57N Rac2 proteins were assayed for direct binding to the GST-TrioN fusion protein. Equal amounts of proteins were used for each lane. Protein was detected on the immunoblot by anti-His-tag antibody. GST alone was used as control in lane 1 . GST-TrioN binds to both WT Rac2 ( lane 2 ) and D57N Rac2 mutant ( lane 3 ) at similar levels. His-Rac2 D57N ( lane 3 ) runs higher because of an 11-residue T7 tag fused to its N terminus. The results shown are representative of three experiments.
FIG. 2 GDP/GTPexchangeofD57NRac2mutantstimulated by guanine nucleotide exchange factor TrioN. Panel A , 2 m g of recombinant WT Rac2 ( circles ) and D57N Rac2 ( triangles ) were preloaded with [ 3 H]GDP and exchanged for cold GTP in the absence ( solid symbols ) or presence ( open symbols ) of 0.5 m g of TrioN. The remaining bound [ 3 H]GDP was determined at 0, 2, 5, 10, and 15 min after GTP exchange. The amount of bound nucleotide at t 5 0 min was set to 100%. The data are presented as the percentage of bound [ 3 H]GDP remaining. The results shown are representative of three experiments. Panel B , binding of guanine nucleotide exchange factor, TrioN, to WT and D57N Rac2. Purified recombinant His-tagged WT Rac2 and D57N Rac2 proteins were assayed for direct binding to the GST-TrioN fusion protein. Equal amounts of proteins were used for each lane. Protein was detected on the immunoblot by anti-His-tag antibody. GST alone was used as control in lane 1 . GST-TrioN binds to both WT Rac2 ( lane 2 ) and D57N Rac2 mutant ( lane 3 ) at similar levels. His-Rac2 D57N ( lane 3 ) runs higher because of an 11-residue T7 tag fused to its N terminus. The results shown are representative of three experiments.CC-BY · From the PDF
Image 3
CC-BY · From the PDF
FIG. 3 Retrovirus-mediated transduction of mouse bone marrow cells with Rac2 retrovirus vectors. Panel A , MIEG3-based retroviral vector was used as a backbone for the Rac2 transgenes. Murine cDNAs encoding WT Flag-tagged Rac2 or mutant Rac2 (D57N and Q61L) was cloned into MIEG3 in front of the internal ribosome re-entry site and EGFP reporter gene. LTR , long terminal repeats; IRES , internal ribosome entry site. Panel B , immunoblot analyses of transduced and EGFP 1 mouse bone marrow cells using antibodies to Rac1, Rac2, Cdc42, and p38 (mitogen-activated protein kinase, as a loading control) proteins. Anti-Rac2 antiserum has weak cross-reaction with Rac1 as seen in lane 2 (MIEG3). The size of the murine WT Rac2 ( lane 3 ) protein is slightly higher because of the Flag tag.
FIG. 3 Retrovirus-mediated transduction of mouse bone marrow cells with Rac2 retrovirus vectors. Panel A , MIEG3-based retroviral vector was used as a backbone for the Rac2 transgenes. Murine cDNAs encoding WT Flag-tagged Rac2 or mutant Rac2 (D57N and Q61L) was cloned into MIEG3 in front of the internal ribosome re-entry site and EGFP reporter gene. LTR , long terminal repeats; IRES , internal ribosome entry site. Panel B , immunoblot analyses of transduced and EGFP 1 mouse bone marrow cells using antibodies to Rac1, Rac2, Cdc42, and p38 (mitogen-activated protein kinase, as a loading control) proteins. Anti-Rac2 antiserum has weak cross-reaction with Rac1 as seen in lane 2 (MIEG3). The size of the murine WT Rac2 ( lane 3 ) protein is slightly higher because of the Flag tag.CC-BY · From the PDF
Image 5
CC-BY · From the PDF
FIG. 4 GTPase activities in the transduced bone marrow cells. Both WT and Rac2 2 / 2 mouse BM cells expressing transgenes MIEG3, WT Rac2, D57N, and Q61L (dominant active mutant Rac2) were used for the PAK1 PBD GST effector pull-down assay. GTP-bound proteins were analyzed by immunoblot using antibodies for Rac2 ( upper panel ) and Rac1 ( lower panel ). Flag-tagged WT Rac2 protein bands were slightly higher ( lanes 2 and 6 , upper panel ). The results shown are representative of four independent experiments.
FIG. 4 GTPase activities in the transduced bone marrow cells. Both WT and Rac2 2 / 2 mouse BM cells expressing transgenes MIEG3, WT Rac2, D57N, and Q61L (dominant active mutant Rac2) were used for the PAK1 PBD GST effector pull-down assay. GTP-bound proteins were analyzed by immunoblot using antibodies for Rac2 ( upper panel ) and Rac1 ( lower panel ). Flag-tagged WT Rac2 protein bands were slightly higher ( lanes 2 and 6 , upper panel ). The results shown are representative of four independent experiments.CC-BY · From the PDF
FIG. 5 Growth of transduced bone marrow cells expressing WT and mutant Rac2 transgenes. Mouse WT LDBM cells were infected with E86 viral supernatant containing retrovirus MIEG3 (vector alone), WT Rac2, and mutants of Rac2 (D57N and Q61L) (for details, see 'Experimental Procedures'). Transduced cells were sorted for EGFP and cultured in liquid RPMI medium ( panel A ) or methyl cellulose ( panel B ) in the presence of G-CSF, SCF, and MGDF (100 ng/ m l each). Panel A , for liquid culture, 1 3 10 5 sorted cells were seeded in the 24-well tissue culture plate on day 5 after transduction. Cell numbers were counted on every other until day 13. *, p , 0.001 MIEG3 versus D57N; **, p , 0.01 WT Rac2 versus MIEG3. Panel B , for the colonyforming assay, 1 3 10 4 /ml transduced and GFP 1 cells (both WT and Rac2 2 / 2 backgrounds) were plated in methyl cellulose and incubated for 7 days. Colony numbers and sizes were determined under an inverted microscope. Colony size was scored from large ( open bars ) to small ( leftside hatched bars ). Data are presented as the mean 6 S.D. of three independent experiments.
FIG. 5 Growth of transduced bone marrow cells expressing WT and mutant Rac2 transgenes. Mouse WT LDBM cells were infected with E86 viral supernatant containing retrovirus MIEG3 (vector alone), WT Rac2, and mutants of Rac2 (D57N and Q61L) (for details, see 'Experimental Procedures'). Transduced cells were sorted for EGFP and cultured in liquid RPMI medium ( panel A ) or methyl cellulose ( panel B ) in the presence of G-CSF, SCF, and MGDF (100 ng/ m l each). Panel A , for liquid culture, 1 3 10 5 sorted cells were seeded in the 24-well tissue culture plate on day 5 after transduction. Cell numbers were counted on every other until day 13. *, p , 0.001 MIEG3 versus D57N; **, p , 0.01 WT Rac2 versus MIEG3. Panel B , for the colonyforming assay, 1 3 10 4 /ml transduced and GFP 1 cells (both WT and Rac2 2 / 2 backgrounds) were plated in methyl cellulose and incubated for 7 days. Colony numbers and sizes were determined under an inverted microscope. Colony size was scored from large ( open bars ) to small ( leftside hatched bars ). Data are presented as the mean 6 S.D. of three independent experiments.CC-BY · From the PDF
Image 8
CC-BY · From the PDF
Image 9
CC-BY · From the PDF
FIG. 6 In vivo engraftment of the transduced hematopoietic stem and progenitor cells. WT mouse bone marrow cells were transduced with retrovirus vectors expressing WT Rac2 ( panel A ) and D57N Rac2 ( panel B ) and transplanted into the lethally irradiated mouse recipients. The level of GFP 1 cells in the peripheral blood of these mice was determined each month by flow cytometry. Each line represents a transplanted animal.
FIG. 6 In vivo engraftment of the transduced hematopoietic stem and progenitor cells. WT mouse bone marrow cells were transduced with retrovirus vectors expressing WT Rac2 ( panel A ) and D57N Rac2 ( panel B ) and transplanted into the lethally irradiated mouse recipients. The level of GFP 1 cells in the peripheral blood of these mice was determined each month by flow cytometry. Each line represents a transplanted animal.CC-BY · From the PDF
FIG. 7 Effect of Rac2 mutants on DNA synthesis and cell apoptosis. WT BM cells expressing empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) were stimulated in the presence of G-CSF, SCF, and MGDF (100 ng/ml each). Untransduced BM cells were also used as the control. Panel A , cell proliferation. [ 3 H]Thymidine was added for 6 h at 37 °C. 5 3 10 4 cells were then harvested on the filter, and b -emissions were measured. Data are presented as the mean 6 S.D. of six independent samples. Panel B , cell apoptosis. 2 3 10 5 cells were collected at different time points after transduction and stained with PE-conjugated annexin V. *, p , 0.003 D57N versus MIEG3. Panel C , TUNEL assay. 2 3 10 6 cells were collected at 7 days after transduction and stained with the in situ cell death detection kit, TMR red (Roche). The percentage apoptosis was determined by FACS analysis. Data are presented as the mean 6 S.D. of three experiments. *, p , 0.003 D57N versus MIEG3. **, p , 0.05 MIEG3 versus WT Rac2 (or Q61L).
FIG. 7 Effect of Rac2 mutants on DNA synthesis and cell apoptosis. WT BM cells expressing empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) were stimulated in the presence of G-CSF, SCF, and MGDF (100 ng/ml each). Untransduced BM cells were also used as the control. Panel A , cell proliferation. [ 3 H]Thymidine was added for 6 h at 37 °C. 5 3 10 4 cells were then harvested on the filter, and b -emissions were measured. Data are presented as the mean 6 S.D. of six independent samples. Panel B , cell apoptosis. 2 3 10 5 cells were collected at different time points after transduction and stained with PE-conjugated annexin V. *, p , 0.003 D57N versus MIEG3. Panel C , TUNEL assay. 2 3 10 6 cells were collected at 7 days after transduction and stained with the in situ cell death detection kit, TMR red (Roche). The percentage apoptosis was determined by FACS analysis. Data are presented as the mean 6 S.D. of three experiments. *, p , 0.003 D57N versus MIEG3. **, p , 0.05 MIEG3 versus WT Rac2 (or Q61L).CC-BY · From the PDF
FIG. 8 Chemotaxis of transduced and in vitro differentiated bone marrow cells. Mouse bone marrow cells (both WT and Rac2 2 / 2 genetic backgrounds) expressing empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) were stimulated to induce myeloid cell differentiation in the presence of G-CSF, SCF, and MGDF (100 ng/ml each) for 7 days. At the time of assay, . 90% of cells were Mac1 1 /Gr-1 1 . Chemotaxis of these cells was examined using a modified Boyden chamber as described under 'Experimental Proceduress.' 1 m M fMLP was used as the chemoattractant. The number of migrating cells on the filter was determined by counting five random 400 3 microscope fields. Data are expressed as the mean number of cells/field 6 S.D. *, p , 0.01 MIEG3 versus WT Rac2 and Q61L Rac2.
FIG. 8 Chemotaxis of transduced and in vitro differentiated bone marrow cells. Mouse bone marrow cells (both WT and Rac2 2 / 2 genetic backgrounds) expressing empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) were stimulated to induce myeloid cell differentiation in the presence of G-CSF, SCF, and MGDF (100 ng/ml each) for 7 days. At the time of assay, . 90% of cells were Mac1 1 /Gr-1 1 . Chemotaxis of these cells was examined using a modified Boyden chamber as described under 'Experimental Proceduress.' 1 m M fMLP was used as the chemoattractant. The number of migrating cells on the filter was determined by counting five random 400 3 microscope fields. Data are expressed as the mean number of cells/field 6 S.D. *, p , 0.01 MIEG3 versus WT Rac2 and Q61L Rac2.CC-BY · From the PDF
FIG. 9 NADPH oxidase activity of transduced and in vitro differentiated myeloid cells. WT and Rac2 2 / 2 BM cells were transduced and express empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) and were differentiated into myeloid cells as in Fig. 8. NADPH oxidase activity of these cells was measured by the NBT test, as described under 'Experimental Procedures.' Cells were stimulated with either 1 m M fMLP ( panel A ) or 100 ng/ml PMA ( panel B ). The percentage of NBT 1 cells on the slide was determined by counting 200 cells in triplicate. Data are expressed as the mean 6 S.D. of three experiments. *, p , 0.005 MIEG3 versus D57N in WT cells; **, p , 0.001 MIEG3 versus D57N in Rac2 2 / 2 cells.
FIG. 9 NADPH oxidase activity of transduced and in vitro differentiated myeloid cells. WT and Rac2 2 / 2 BM cells were transduced and express empty vector (MIEG3), WT Rac2, and mutants of Rac2 (D57N and Q61L) and were differentiated into myeloid cells as in Fig. 8. NADPH oxidase activity of these cells was measured by the NBT test, as described under 'Experimental Procedures.' Cells were stimulated with either 1 m M fMLP ( panel A ) or 100 ng/ml PMA ( panel B ). The percentage of NBT 1 cells on the slide was determined by counting 200 cells in triplicate. Data are expressed as the mean 6 S.D. of three experiments. *, p , 0.005 MIEG3 versus D57N in WT cells; **, p , 0.001 MIEG3 versus D57N in Rac2 2 / 2 cells.CC-BY · From the PDF
Image 14
CC-BY · From the PDF
FIG. 10 Expression and activity of endogenous Rac1 GTPase in Rac2 2 / 2 BM cells. Low density BM cells were extracted from the littermates of WT and Rac2 2 / 2 mice. Fresh BM cells were either assayed directly or cultured in vitro in a complete RPMI medium (see 'Experimental Procedures') for 7 days and then used for immunoblots and PAK1 PBD GST effector pull-down assay. Whole cell lysate ( panel A ) and GTP-bound proteins ( panel B ) were analyzed by immunoblot using antibodies for Rac1 and total p38. The results shown are representative of three independent experiments.
FIG. 10 Expression and activity of endogenous Rac1 GTPase in Rac2 2 / 2 BM cells. Low density BM cells were extracted from the littermates of WT and Rac2 2 / 2 mice. Fresh BM cells were either assayed directly or cultured in vitro in a complete RPMI medium (see 'Experimental Procedures') for 7 days and then used for immunoblots and PAK1 PBD GST effector pull-down assay. Whole cell lysate ( panel A ) and GTP-bound proteins ( panel B ) were analyzed by immunoblot using antibodies for Rac1 and total p38. The results shown are representative of three independent experiments.CC-BY · From the PDF

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References 48 · Cited by 100

Research works printed but not linked: 6

  1. Williams, 2000, Blood, 96, 1646
  2. Shirsat, 1990, Oncogene, 5, 769
  3. Moll, 1991, Oncogene, 6, 863
  4. Bjorgvinsdottir, 1997, Blood, 89, 41, 10.1182/blood.V89.1.41 · DOI
  5. Jung, 1994, Mol. Cell. Biol., 14, 3707
  6. Felts, 1999, strategies, 12, 74

Metadata

Authors
Gu, Y., Jia, B., Yang, F.-C., D'Souza, M., Harris, C. E., Derrow, C. W., Zheng, Y., & Williams, D. A.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of Tennessee Health Science Center (US)
  • Indiana University Indianapolis (US)
Corresponding author
Williams, David A.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-05
Volume
276
Issue
19
Pages
15929-15938
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m010445200
OpenAlex
W2033931111
Semantic Scholar
341d6a480a29e5de7d5a412ddc9f6ceb84af8893
Cited by
100
References
48
Citations by year
2026: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 4 · 2012: 2
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM060523)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
Rac2, Rho GTPases, dominant negative mutation, neutrophil chemotaxis, GTP binding, guanine nucleotide exchange factor, Rac1, apoptosis, cell proliferation, bone marrow transplantation, neutrophil migration, superoxide production, hematopoietic cells
MeSH terms
RAC2 GTP-Binding Protein, Animals, Bone Marrow Cells, Cell Division, Cell Line, Cell Survival, Cloning, Molecular, Guanosine Diphosphate, Guanosine Triphosphate, Hematopoietic Stem Cells, Humans, Immunologic Deficiency Syndromes, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Phagocytosis, Phenotype, Recombinant Proteins, Superoxides, Transfection, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Amino Acid Substitution, GTP Phosphohydrolases, rac GTP-Binding Proteins, Mice

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Gu, Y., Jia, B., Yang, F.-C., D'Souza, M., Harris, C. E., Derrow, C. W., Zheng, Y., & Williams, D. A. (2001). Biochemical and Biological Characterization of a Human Rac2 GTPase Mutant Associated with Phagocytic Immunodeficiency. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m010445200