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PMID:7889565

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Citation

Voncken, JW, van Schaick, H, Kaartinen, V, Deemer, K, Coates, T, Landing, B, Pattengale, P, Dorseuil, O, Bokoch, GM and Groffen, J (1995) Increased neutrophil respiratory burst in bcr-null mutants. Cell 80:719-28

Abstract

Philadelphia (Ph)-positive leukemias invariably contain a chromosomal translocation fusing BCR to ABL. The BCR-ABL protein is responsible for leukemogenesis. Here we show that exposure of bcr-null mutant mice to gram-negative endotoxin led to severe septic shock and increased tissue injury by neutrophils. Neutrophils of bcr (-/-) mice showed a pronounced increase in reactive oxygen metabolite production upon activation and were more sensitive to priming stimuli. Activated (-/-) neutrophils displayed a 3-fold increased p21rac2 membrane translocation compared with (+/+) neutrophils. These results connect Bcr in vivo with the regulation of Rac-mediated superoxide production by the NADPH-oxidase system of leukocytes and suggest a link between Bcr function and the cell type affected in Ph-positive leukemia.

Links

PubMed

Keywords

Actin Cytoskeleton/physiology; Animals; Endotoxins/toxicity; Female; GTP-Binding Proteins/biosynthesis; GTP-Binding Proteins/metabolism; Gene Targeting; Lipopolysaccharides/pharmacology; Male; Mice; Mice, Inbred C57BL; Mutation/physiology; Neutropenia/chemically induced; Neutropenia/immunology; Neutrophil Activation; Neutrophils/metabolism; Oncogene Proteins/genetics; Oncogene Proteins/physiology; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcr; Respiratory Burst/immunology; Shock, Septic/chemically induced; Shock, Septic/immunology; Shock, Septic/pathology; Superoxides/metabolism; Toxemia/chemically induced; Toxemia/immunology; Toxemia/pathology; rac GTP-Binding Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BCR

acts_upstream_of_or_within

GO:0003014: renal system process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0048872: homeostasis of number of cells

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0051171: regulation of nitrogen compound metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0060268: negative regulation of respiratory burst

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:2000378: negative regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0071222: cellular response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

MOUSE:BCR

acts_upstream_of_or_within

GO:0065002: intracellular protein transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154396

P

Seeded From UniProt

complete

Notes

See also

References

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