title: Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).
abstract: Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Melissa
authors.initials: M
authors.lastname: Branham-O'Connor
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: William G
authors.initials: WG
authors.lastname: Robichaux
authors.affiliation: Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Xian-Kui
authors.initials: XK
authors.lastname: Zhang
authors.affiliation: B-cell Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Hyeseon
authors.initials: H
authors.lastname: Cho
authors.affiliation: B-cell Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lanier
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425. Electronic address: blumerjb@musc.edu.
authors.forename: Joe B
authors.initials: JB
authors.lastname: Blumer
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors; D007107:Immune System; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D060168:Thymocytes / Q000166:cytology
chemical_list: D002352:Carrier Proteins; D018925:Chemokines; C498915:Gpsm1 protein, mouse; D020730:Guanine Nucleotide Dissociation Inhibitors; D019204:GTP-Binding Proteins; D002118:Calcium
keywords: AGS3; Chemokines; Chemotaxis; Cxcr4; G Proteins; G-protein-coupled Receptors (GPCR); GPR Motif; Gpsm1; Gαi; Gβγ