IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family members.
Activation of the high-affinity IgE-receptor, FcepsilonRI, expressed on mast cells can result in either enhanced survival or apoptosis depending on the circumstances. In this study, we have analysed signalling pathways involved in the regulation of mast cell survival and apoptosis. FcepsilonRI cross-linking induces phosphorylation of Akt and its downstream target forkhead transcription factors. In addition, Bad, GSK-3beta and IkappaB-alpha also become phosphorylated. A1, a prosurvival Bcl-2 homologue transcriptionally controlled by NFkappaB transcription factors, is upregulated upon FcepsilonRI activation. These events have prosurvival effects on the mast cells. Moreover, FcepsilonRI activation upregulates the levels of the proapoptotic protein Bim and induces a rapid, but transient, phosphorylation of Bim. Thus, FcepsilonRI activation of mast cells leads to both prosurvival and proapoptotic signalling events where the outcome most likely depends on the balance between these signals.
Alfredsson
J
J
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Möller
C
C
Nilsson
G
G
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020672:I-kappa B Proteins / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494820:Bad protein, mouse; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D051858:Forkhead Transcription Factors; D020672:I-kappa B Proteins; D008565:Membrane Proteins; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D051025:bcl-Associated Death Protein; D000072000:NF-KappaB Inhibitor alpha; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3