Control of Pre-BCR Signaling by Pax5-Dependent Activation of the BLNK Gene
Copyright policy )Control of Pre-BCR Signaling by Pax5-Dependent Activation of the BLNK Gene
The developmental progression from pro-B to pre-B cells is controlled by pre-B cell receptor (pre-BCR) signaling which depends on BLNK (SLP-65) for coupling the Syk kinase to its downstream effector pathways. Here we identified BLNK as a direct target of the transcription factor Pax5 (BSAP). Restoration of BLNK expression in Ig(mu) transgenic Pax5(-/-) pro-B cells resulted in constitutive pre-BCR signaling and increased cell proliferation without inducing progression to the pre-B cell stage. Ig(mu)(+) Pax5(-/-) pro-B cells expressing a BLNK-estrogen receptor fusion protein initiated signaling immediately upon hormone addition, which facilitated analysis of pre-BCR-induced gene expression changes. The pre-BCR was shown to execute its checkpoint function by regulating genes involved in cell proliferation, intracellular signaling, growth factor responsiveness, and V(D)J recombination.
- Crown Research Institutes New Zealand
- Vienna Biocenter Austria
- Research Institute of Molecular Pathology Austria
DNA, Complementary, Immunology, Molecular Sequence Data, Mice, Transgenic, Mice, Immunology and Allergy, Animals, Calcium Signaling, Adaptor Proteins, Signal Transducing, Mice, Knockout, B-Lymphocytes, Binding Sites, Base Sequence, Immunoglobulin mu-Chains, Phospholipase C gamma, Lymphopoiesis, PAX5 Transcription Factor, Hematopoietic Stem Cells, DNA-Binding Proteins, Isoenzymes, Infectious Diseases, Gene Expression Regulation, Carrier Proteins
DNA, Complementary, Immunology, Molecular Sequence Data, Mice, Transgenic, Mice, Immunology and Allergy, Animals, Calcium Signaling, Adaptor Proteins, Signal Transducing, Mice, Knockout, B-Lymphocytes, Binding Sites, Base Sequence, Immunoglobulin mu-Chains, Phospholipase C gamma, Lymphopoiesis, PAX5 Transcription Factor, Hematopoietic Stem Cells, DNA-Binding Proteins, Isoenzymes, Infectious Diseases, Gene Expression Regulation, Carrier Proteins
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