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Phosphatidylinositol 3-kinase is required for the transcriptional activation of cyclin D2 in BCR activated primary mouse B lymphocytes.
- Source :
-
European journal of immunology [Eur J Immunol] 2005 Sep; Vol. 35 (9), pp. 2748-61. - Publication Year :
- 2005
-
Abstract
- Induction of cyclin D2 is essential for mediating cell cycle entry in B cells activated by BCR cross-linking. In the present study we show that, like B lymphocytes lacking cyclin D2, the p85alpha subunit of phosphatidylinositol 3-kinase (PI3K) or other components of the B cell signalosome, p110delta-null B cells fail to induce cyclin D2 and enter early G1 but not S phase of the cell cycle. The inhibitors of PI3K activity, LY294002 and Wortmannin, also abrogate cyclin D2 induction by BCR cross-linking, confirming that the class IA PI3K is necessary for cyclin D2 induction in response to BCR stimulation. Furthermore, using both p85alpha-null and p110delta-null B cells and inhibitors of PI3K, this study demonstrates for the first time, that BCR cross-linking induces cyclin D2 mRNA expression via transcriptional activation of the cyclin D2 promoter and that this transcriptional activation of cyclin D2 requires PI3K activity. Moreover, we identify a region between nucleotides -1624 and -1303 of the cyclin D2 promoter containing elements responsive to anti-IgM, which are PI3K dependent. Further characterisation of signalling intermediates downstream of the BCR revealed a perturbation of MAPK signalling pathways in p85alpha-null and p110delta-null B cells, and our data suggests that cross-talk exists between the PI3K and JNK pathways.
- Subjects :
- Androstadienes pharmacology
Animals
B-Lymphocytes enzymology
B-Lymphocytes immunology
Blotting, Western
Cell Cycle immunology
Chromones pharmacology
Class I Phosphatidylinositol 3-Kinases
Cyclin D2
Cyclins genetics
Cyclins immunology
Lymphocyte Activation immunology
Mice
Mice, Knockout
Morpholines pharmacology
Phosphatidylinositol 3-Kinases immunology
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors pharmacology
RNA chemistry
RNA genetics
Receptors, Antigen, B-Cell immunology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction immunology
Transcriptional Activation
Wortmannin
B-Lymphocytes physiology
Cyclins physiology
Phosphatidylinositol 3-Kinases physiology
Receptors, Antigen, B-Cell physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 35
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16114097
- Full Text :
- https://doi.org/10.1002/eji.200425812