FcgammaRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization
Autor: | W A, Jensen, S, Marschner, V L, Ott, J C, Cambier |
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Rok vydání: | 2001 |
Předmět: |
Time Factors
T-Lymphocytes Immunoblotting Receptors IgG Receptors Antigen T-Cell Membrane Proteins Flow Cytometry Phosphoproteins Precipitin Tests Phosphoric Monoester Hydrolases Cell Line Enzyme Activation Mice Antigens CD Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Animals Tyrosine Calcium Phosphorylation Carrier Proteins Adaptor Proteins Signal Transducing Protein Binding Signal Transduction |
Zdroj: | Biochemical Society transactions. 29(Pt 6) |
ISSN: | 0300-5127 |
Popis: | The low-affinity receptor for immunoglobulin G, FcgammaRIIB, is expressed on most B-cells and on immature and activated mature T-cells. Co-aggregation of FcgammaRIIB with the B-cell antigen receptor (BCR) leads to attenuation of BCR-induced blastogenesis and cell proliferation via inhibition of p21(ras), phosphatidylinositol 3-kinase (PI3-K) and phospholipase Cgamma (PLCgamma) activation. These effects are mediated, at least in part, by the recruitment of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and -2 (SHP-2) and SH2-containing inositol 5-phosphatase (SHIP). In this report, we demonstrate that FcgammaRIIB co-aggregation with the T-cell antigen receptor (TCR), which may occur when T-cells recognize antibody-coated target cells, leads to inhibition of TCR-induced phosphorylation of the linker of activated T-cells (LAT). When phosphorylated, LAT functions as an adapter molecule and recruits PI3-K. Additionally, we demonstrate that PI3-K is required for TCR-induced Ca(2+) mobilization. Together, these data suggest that FcgammaRIIB may inhibit TCR-mediated Ca(2+) mobilization, in part via inhibition of LAT phosphorylation and subsequent inhibition of PI3-K activation. A similar mechanism has been described in B-cells, where FcgammaRIIB co-aggregation with the BCR leads to inhibition of PI3-K activity via dephosphorylation of CD19. It is likely that, in both cell types, levels of PtdIns(3,4,5)P(3) are additionally modulated via the enzymic activity of SHIP. |
Databáze: | OpenAIRE |
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