| pubmed-article:16092944 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0027882 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0007765 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0010837 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0521451 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0018296 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C1444748 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C1707310 | lld:lifeskim |
| pubmed-article:16092944 | lifeskim:mentions | umls-concept:C1516044 | lld:lifeskim |
| pubmed-article:16092944 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:16092944 | pubmed:dateCreated | 2005-8-11 | lld:pubmed |
| pubmed-article:16092944 | pubmed:abstractText | Rho GTPases are key transducers of integrin/extracellular matrix and growth factor signaling. Although integrin-mediated adhesion and trophic support suppress neuronal apoptosis, the role of Rho GTPases in neuronal survival is unclear. Here, we have identified Rac as a critical pro-survival GTPase in cerebellar granule neurons (CGNs) and elucidated a death pathway triggered by its inactivation. GTP-loading of Rac1 was maintained in CGNs by integrin-mediated (RGD-dependent) cell attachment and trophic support. Clostridium difficile toxin B (ToxB), a specific Rho family inhibitor, induced a selective caspase-mediated degradation of Rac1 without affecting RhoA or Cdc42 protein levels. Both ToxB and dominant-negative N17Rac1 elicited CGN apoptosis, characterized by cytochrome c release and activation of caspase-9 and -3, whereas dominant-negative N19RhoA or N17Cdc42 did not cause significant cell death. ToxB stimulated mitochondrial translocation and conformational activation of Bax, c-Jun activation, and induction of the BH3-only protein Bim. Similarly, c-Jun activation and Bim induction were observed with N17Rac1. A c-jun N-terminal protein kinase (JNK)/p38 inhibitor, SB203580, and a JNK-specific inhibitor, SP600125, significantly decreased ToxB-induced Bim expression and blunted each subsequent step of the apoptotic cascade. These results indicate that Rac acts downstream of integrins and growth factors to promote neuronal survival by repressing c-Jun/Bim-mediated mitochondrial apoptosis. | lld:pubmed |
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| pubmed-article:16092944 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16092944 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16092944 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16092944 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16092944 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:16092944 | pubmed:issn | 0022-3042 | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:AktoriesKlaus... | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:BarthHolgerH | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:LinsemanDanie... | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:UdoHiroshiH | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:KandelEric... | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:HeidenreichKi... | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:TylerKenneth... | lld:pubmed |
| pubmed-article:16092944 | pubmed:author | pubmed-author:BouchardRon... | lld:pubmed |
