title: LyGDI, a novel SHIP-interacting protein, is a negative regulator of FcγR-mediated phagocytosis.
abstract: SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis.
authors.affiliation: The Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Payal
authors.initials: P
authors.lastname: Mehta
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Wavreille
authors.forename: Steven E
authors.initials: SE
authors.lastname: Justiniano
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Marsh
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Richard W
authors.initials: RW
authors.lastname: Burry
authors.forename: David
authors.initials: D
authors.lastname: Jarjoura
authors.forename: Timothy
authors.initials: T
authors.lastname: Eubank
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Butchar
authors.forename: Susheela
authors.initials: S
authors.lastname: Tridandapani
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011392:Proline; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017452:Receptors, IgG / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569658:ARHGDIB protein, human; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D017452:Receptors, IgG; D055765:Shc Signaling Adaptor Proteins; D025521:Tumor Suppressor Proteins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D011392:Proline; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D020744:rac GTP-Binding Proteins