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Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2.

Nature immunology | Jul 20, 2006

http://www.ncbi.nlm.nih.gov/pubmed/16715100

In neutrophils, superoxide anion production generally accompanies chemotaxis and functions in killing invading pathogens. The GIT2 GTPase-activating protein binds to the guanine nucleotide-exchange factor alphaPIX. Here we show that GIT2 was necessary for directional chemotaxis and for the suppression of superoxide production in G protein-coupled receptor-stimulated neutrophils. GIT2 was also necessary for the orientation of superoxide production toward chemoattractant sources. GIT2 suppressed the activity of ADP ribosylation factor 1 and was a component of the Gbetagamma subunit-mediated direction-sensing machinery 'downstream' of G protein-coupled receptor signaling. This study establishes a function for GIT2 in linking chemotaxis and superoxide production in neutrophils and shows that loss of GIT2 in vivo leads to an immunodeficient state.

Pubmed ID: 16715100 RIS Download

Mesh terms: ADP-Ribosylation Factor 1 | Actins | Animals | Aspergillosis | Cell Cycle Proteins | Chemotactic Factors | Chemotaxis | Complement C5a | Disease Susceptibility | Enzyme Activation | GTP-Binding Protein beta Subunits | GTP-Binding Protein gamma Subunits | Guanine Nucleotide Exchange Factors | Immunologic Deficiency Syndromes | Interleukin-8 | Lung | Lung Diseases, Fungal | Mice | Mice, Inbred C57BL | Mice, Knockout | Multiprotein Complexes | N-Formylmethionine Leucyl-Phenylalanine | Neutrophils | Phosphatidylinositol Phosphates | Phosphoproteins | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins c-akt | Receptors, G-Protein-Coupled | Recombinant Fusion Proteins | Rho Guanine Nucleotide Exchange Factors | Superoxides | p21-Activated Kinases | rac1 GTP-Binding Protein

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