B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins

Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and anti-...

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Vydané v:	Cellular signalling Ročník 21; číslo 4; s. 609 - 621
Hlavní autori:	Grandoch, Maria, López de Jesús, Maider, Oude Weernink, Paschal A., Weber, Artur-Aron, Jakobs, Karl H., Schmidt, Martina
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England Elsevier Inc 01.04.2009
Predmet:	Adenylyl Cyclase Inhibitors Animals Apoptosis Apoptosis - physiology B cells Bacterial Toxins - pharmacology Carrier Proteins - physiology Cell Division - physiology Cell Line, Tumor - drug effects Cell Line, Tumor - enzymology Cyclic AMP Cyclic AMP - physiology Enzyme Activation Exchange protein directly activated by cyclic AMP Extracellular signal-regulated kinases Guanine Nucleotide Exchange Factors - physiology Lymphoma, B-Cell - pathology Mice Mitogen-Activated Protein Kinase 1 - physiology Mitogen-Activated Protein Kinase 3 - physiology Monomeric GTPases Phosphorylation Protein kinase B/Akt Protein Processing, Post-Translational Proto-Oncogene Proteins c-akt - physiology Proto-Oncogene Proteins p21(ras) - physiology rap1 GTP-Binding Proteins - physiology Receptors, Antigen, B-Cell - physiology Signal Transduction - physiology Exchange protein directly activated by cyclic AMP Protein kinase B/Akt Extracellular signal-regulated kinases Monomeric GTPases Cyclic AMP B cells Apoptosis
ISSN:	0898-6568, 1873-3913, 1873-3913
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Shrnutí:	Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and anti-apoptotic phosphoinositide 3-kinase-dependent Akt seems to define the final cellular apoptotic response. Dysfunction of these late BCR signaling events can lead to the development of immunological diseases. Here we report on novel cyclic AMP-dependent mechanisms of BCR-induced growth arrest and apoptosis in the immature B lymphoma cell line WEHI-231. BCR signaling to ERK1/2 and Akt requires cyclic AMP-regulated Epac, the latter acting as a guanine nucleotide exchange factor for Rap1 and H-Ras independent of protein kinase A. Importantly, activation of endogenously expressed Epac by a specific cyclic AMP analog enhanced the induction of growth arrest (reduced DNA synthesis) and apoptosis (nuclear condensation, annexin V binding, caspase-3 cleavage and poly-ADP-ribose polymerase processing) by the BCR. Our data indicate that cyclic AMP-dependent Epac signals to ERK1/2 and Akt upon activation of Rap1 and H-Ras, and is involved in BCR-induced growth arrest and apoptosis in WEHI-231 cells.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0898-6568 1873-3913 1873-3913
DOI:	10.1016/j.cellsig.2009.01.002