| http://purl.uniprot.org/citations/14615375 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14615375 | http://www.w3.org/2000/01/rdf-schema#comment | "Type 4 cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE4) inhibitors and other agents that raise intracellular cAMP levels induce apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) but not in T-CLL or peripheral blood T cells. Two principal effector proteins for cAMP are protein kinase A (PKA) and EPAC (exchange protein directly activated by cAMP), a Rap guanosine 5'-diphosphate (GDP) exchange factor. We here examine whether varying expression of EPAC accounts for the discrepant sensitivity of B-CLL and T cells to PDE4 inhibitor-induced apoptosis. B-CLL and peripheral blood B cells express EPAC1 transcript, whereas T-CLL, peripheral blood T cells, monocytes, and neutrophils do not. Treatment with the PDE4 inhibitor rolipram induces Rap1 activation in B-CLL cells but not in peripheral blood B cells, T-CLL, or any of the normal hematopoietic lineages examined. The EPAC-specific cAMP analog 8CPT-2Me-cAMP (8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cAMP) activates Rap1 in B-CLL cells, but, unlike rolipram/forskolin or 8-Bromo-cAMP, it does not induce PKA activation, as judged by phosphorylation of the transcription factor cAMP-response element binding protein (CREB). Unexpectedly, whereas rolipram/forskolin and 8-Bromo-cAMP induce apoptosis in B-CLL cells, 8CPT-2Me-cAMP decreased basal apoptosis in B-CLL cells by an average of 25% (P<.002). Our results demonstrate that B-CLL cells uniquely activate Rap1 in response to PDE4 inhibitors and suggest that physiologic stimuli that activate EPAC may transmit an antiapoptotic signal."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2003-06-2154"xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Tiwari S."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Lerner A."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Moon E.Y."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Sherr D.H."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Felekkis K."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/author | "Flies A."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/pages | "2661-2667"xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/title | "Among circulating hematopoietic cells, B-CLL uniquely expresses functional EPAC1, but EPAC1-mediated Rap1 activation does not account for PDE4 inhibitor-induced apoptosis."xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://purl.uniprot.org/core/volume | "103"xsd:string |
| http://purl.uniprot.org/citations/14615375 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/14615375 |
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