Src-like adaptor protein (SLAP) is upregulated in antigen-stimulated mast cells and acts as a negative regulator.
Our studies in the RBL-2H3 mast cell line suggest that responses to antigen (Ag) are negatively modulated through upregulation of Src-like adaptor protein (SLAP). Ag stimulation of RBL-2H3 cells leads to increased levels of SLAP (but not SLAP2) transcripts and protein over a period of several hours. The effects of pharmacologic inhibitors indicate that the upregulation of SLAP is dependent on multiple signaling pathways. Knockdown of SLAP with anti-SLAP siRNA is associated with enhanced phosphorylation of Syk, the linker for activation of T cells (LAT), phospholipase C gamma, MAP kinases, and various transcription factors. Production of IL-3 and MCP-1, but not degranulation, is also enhanced. The upregulation of SLAP may thus serve to limit the duration of cytokine production in Ag-stimulated cells.
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Seung-Kiel
SK
Park
Huihong
H
Qiao
Michael A
MA
Beaven
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000941:Antigens / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D016207:Cytokines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017455:Receptors, IgE