Role of phospholipase C-L2, a novel phospholipase C-like protein that lacks lipase activity, in B-cell receptor signaling.
Phospholipase C (PLC) plays important roles in phosphoinositide turnover by regulating the calcium-protein kinase C signaling pathway. PLC-L2 is a novel PLC-like protein which lacks PLC activity, although it is very homologous with PLC delta. PLC-L2 is expressed in hematopoietic cells, but its physiological roles and intracellular functions in the immune system have not yet been clarified. To elucidate the physiological function of PLC-L2, we generated mice which had a genetic PLC-L2 deficiency. PLC-L2-deficient mice grew with no apparent abnormalities. However, mature B cells from PLC-L2-deficient mice were hyperproliferative in response to B-cell receptor (BCR) cross-linking, although B2 cell development appeared to be normal. Molecular biological analysis revealed that calcium influx and NFATc accumulation in nuclei were increased in PLC-L2-deficient B cells. Extracellular signal-regulated kinase activity was also enhanced in PLC-L2-deficient B cells. These mice had a stronger T-cell-independent antigen response. These results indicate that PLC-L2 is a novel negative regulator of BCR signaling and immune responses.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015139:Blotting, Southern; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008957:Models, Genetic; D016296:Mutagenesis; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010641:Phenotype; D010740:Phospholipases / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C530633:Plcl2 protein, mouse; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D010740:Phospholipases; D008049:Lipase; D002118:Calcium