Genes up-regulated in HMC-1 (mast leukemia) cells: Cl-IB-MECA [PubChem=3035850] versus incubated with the ALL1 peptide followed by treatment with Cl-IB-MECA [PubChem=3035850].
Full description or abstract
We demonstrate that the G protein Gi3 is the cellular target of the adenosine A3 receptor (A3R). By using a cell permeable peptide comprising the C-terminal end of G?i3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling, we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines and growth factors.Following contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological GPCR that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells. We used microarrays to detail the effect of ALL1 on gene expression of HMC-1 cells activated directly by the A3 receptor, or by contact with activated T cell membranes.
