Open AccessLyGDI, a Novel SHIP-Interacting Protein, Is a Negative Regulator of FcγR-Mediated Phagocytosis
Author(s) -
Preeti Mehta,
AnneSophie Wavreille,
Steven E. Justiniano,
Rachel Marsh,
Jianhua Yu,
Richard W. Burry,
David Jarjoura,
Timothy D Eubank,
Michael A. Caligiuri,
Jonathan P. Butchar,
Susheela Tridandapani
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0021175
Subject(s) - phagocytosis , microbiology and biotechnology , grb2 , recombinant dna , cytosol , phagosome , chemistry , biology , biochemistry , signal transduction , signal transducing adaptor protein , enzyme , gene
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.