| http://purl.uniprot.org/citations/12700661 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12700661 | http://www.w3.org/2000/01/rdf-schema#comment | "The p85alpha subunit of PI3-K and Btk are two crucial components of the B-cell receptor (BCR) signalling pathway. In the present study, we showed that primary splenic B cells from p85alpha null and xid (Btk-deficient) mice fail to induce cyclin D2 expression and enter early G1, but not S phase of the cell cycle in response to BCR engagement. Furthermore, these Btk or p85alpha null B cells displayed increased cell death compared with wild type following BCR engagement. These findings are further confirmed by studies showing that specific pharmacological inhibitors of Btk (LFM-A13), PI3-K (LY294002 and Wortmannin) and PLCgamma (U73122) also block cyclin D2 expression and S phase entry following BCR stimulation, as well as triggering apoptosis. Collectively, these data provide evidence for the concept that the B-cell signalosome (p85alpha, Btk, BLNK and PLCgamma) is involved in regulating cyclin D2 expression in response to BCR engagement. PKC and intracellular calcium are two major downstream effectors of the B-cell signalosome and can be activated by PMA and ionomycin, respectively. In small resting (G0) B cells, costimulation with PMA and ionomycin, but not PMA or ionomycin alone, induces cyclin D2 expression and cell-cycle progression. Consistent with this, we also showed that the BCR-mediated cyclin D2 induction could be abolished by pretreatment of resting B cells with specific inhibitors of capacitative Ca(2+) entry (SK&F 96365) or PKC (Gö6850). Our present results lead us to propose a model in which the B-cell signalosome targets cyclin D2 via the Ca(2+) and PKC-dependent signalling cascades to mediate cell-cycle progression in response to BCR engagement."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.onc.1206425"xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Kadowaki T."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Holman M."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Lam E.W."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Koyasu S."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Klaus G.G."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Banerji L."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Glassford J."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Skarell S.M."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/author | "Soeiro I."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/pages | "2248-2259"xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/title | "BCR targets cyclin D2 via Btk and the p85alpha subunit of PI3-K to induce cell cycle progression in primary mouse B cells."xsd:string |
| http://purl.uniprot.org/citations/12700661 | http://purl.uniprot.org/core/volume | "22"xsd:string |
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