Linked Life Data

12370370

Source:http://linkedlifedata.com/resource/pubmed/id/12370370

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-10-8
pubmed:abstractText
FcgammaR-mediated phagocytosis is accompanied by the generation of tissue-damaging products such as inflammatory cytokines and reactive oxygen species. Hence, the phagocytic response must be a tightly regulated process. Recent studies have established that clustering FcgammaR on human myeloid cells causes tyrosine phosphorylation of Src homology 2 domain-containing inositol polyphosphate phosphatase (SHIP). However, it is not known how these immunoreceptor tyrosine-based activation motif (ITAM)-bearing phagocytic FcgammaR activate SHIP, or whether the activation of SHIP by ITAMs has any functional relevance. Experiments addressing the mechanism of SHIP association with ITAMs have been done in in vitro systems using phosphopeptides. In this study we undertook to dissect the molecular mechanism by which SHIP associates with the native ITAM-FcgammaR and becomes phosphorylated. In this report we provide evidence that first, SHIP is indeed phosphorylated by ITAM-FcgammaR, using cell systems that lack FcgammaRIIb expression; second, coimmunoprecipitation experiments demonstrate that SHIP associates with native ITAM-bearing FcgammaRIIa in vivo; and third, phosphorylation of SHIP by FcgammaRIIa is inhibited by overexpressing either the SHIP Src homology 2 domain or a dominant negative mutant of Shc. In contrast, SHIP phosphorylation was not inhibited by a dominant negative mutant of Grb2. We extend these observations to show that SHIP activation by ITAM-FcgammaR down-regulates NF-kappaB-induced gene transcription. These findings both provide a molecular mechanism for SHIP association with native ITAM-bearing receptors and demonstrate that SHIP association with ITAM-FcgammaR serves to regulate gene expression during the phagocytic process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4370-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12370370-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12370370-Amino Acid Motifs, pubmed-meshheading:12370370-Animals, pubmed-meshheading:12370370-COS Cells, pubmed-meshheading:12370370-Cells, Cultured, pubmed-meshheading:12370370-GRB2 Adaptor Protein, pubmed-meshheading:12370370-Humans, pubmed-meshheading:12370370-Leukemia P388, pubmed-meshheading:12370370-Lymphocyte Activation, pubmed-meshheading:12370370-Macrophages, pubmed-meshheading:12370370-Mice, pubmed-meshheading:12370370-Myeloid Cells, pubmed-meshheading:12370370-NF-kappa B, pubmed-meshheading:12370370-Phagocytosis, pubmed-meshheading:12370370-Phosphoric Monoester Hydrolases, pubmed-meshheading:12370370-Phosphorylation, pubmed-meshheading:12370370-Precipitin Tests, pubmed-meshheading:12370370-Proteins, pubmed-meshheading:12370370-Receptors, IgG, pubmed-meshheading:12370370-Transcription, Genetic, pubmed-meshheading:12370370-Transfection, pubmed-meshheading:12370370-Tumor Cells, Cultured, pubmed-meshheading:12370370-Tyrosine, pubmed-meshheading:12370370-src Homology Domains
pubmed:year
2002
pubmed:articleTitle
Src homology 2 domain-containing inositol polyphosphate phosphatase regulates NF-kappa B-mediated gene transcription by phagocytic Fc gamma Rs in human myeloid cells.
pubmed:affiliation
Department of Internal Medicine, Heart and Lung Research Institute, Room 405D, Ohio State University, 473 West Twelfth Avenue, Columbus, OH 43210, USA. tridandapani.2@osu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't