RGD Reference Report - Phospholipid scramblase 1 modulates a selected set of IgE receptor-mediated mast cell responses through LAT-dependent pathway. - Rat Genome Database

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Phospholipid scramblase 1 modulates a selected set of IgE receptor-mediated mast cell responses through LAT-dependent pathway.

Authors: Amir-Moazami, O  Alexia, C  Charles, N  Launay, P  Monteiro, RC  Benhamou, M 
Citation: Amir-Moazami O, etal., J Biol Chem. 2008 Sep 12;283(37):25514-23. Epub 2008 Jun 25.
RGD ID: 2303650
Pubmed: PMID:18579528   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M705320200   (Journal Full-text)

Engagement of the IgE receptor (FcepsilonRI) on mast cells leads to the release of preformed and newly formed mediators as well as of cytokines. The signaling pathways responsible for these responses involve tyrosine phosphorylation of multiple proteins. We previously reported the phosphorylation on tyrosine of phospholipid scramblase 1 (PLSCR1) after FcepsilonRI aggregation. Here, PLSCR1 expression was knocked down in the RBL-2H3 mast cell line using short hairpin RNA. Knocking down PLSCR1 expression resulted in significantly impaired degranulation responses after FcepsilonRI aggregation and release of vascular endothelial growth factor, whereas release of MCP-1 was minimally affected. The release of neither leukotriene C4 nor prostaglandin D2 was altered by knocking down of PLSCR1. Analysis of FcepsilonRI-dependent signaling pathways revealed that whereas tyrosine phosphorylation of ERK and Akt was unaffected, tyrosine phosphorylation of LAT was significantly reduced in PLSCR1 knocked down cells. Tyrosine phosphorylation of phospholipase Cgamma1 and consequently the mobilization of calcium were also significantly reduced in these cells. In nonactivated mast cells, PLSCR1 was found in part in lipid rafts where it was further recruited after cell activation and was constitutively associated with Lyn and Syk but not with LAT or Fyn. Altogether, these data identify PLSCR1 as a novel amplifier of FcepsilonRI signaling that acts selectively on the Lyn-initiated LAT/phospholipase Cgamma1/calcium axis, resulting in potentiation of a selected set of mast cell responses.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Plscr1Ratregulation of Fc receptor mediated stimulatory signaling pathway involved_inIMP PMID:18579528UniProt 
Plscr1Ratregulation of mast cell activation involved_inIMP PMID:18579528UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Plscr1Ratmembrane raft located_inIDA PMID:18579528UniProt 
Plscr1Ratplasma membrane located_inIDA PMID:18579528UniProt 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Lyn  (LYN proto-oncogene, Src family tyrosine kinase)
Plscr1  (phospholipid scramblase 1)
Syk  (spleen associated tyrosine kinase)


Additional Information