RRC ID |
43123
|
著者 |
Chaigne-Delalande B, Anies G, Kramer I, Genot E.
|
タイトル |
Nonadherent cells switch to a Rac-mediated, SHIP regulated, Akt activation mode for survival.
|
ジャーナル |
Oncogene
|
Abstract |
Constitutively active Rac stimulates Akt activity in T lymphocytes cultured in suspension. This regulation contrasts with findings obtained in fibroblasts, endothelial or neuronal cells grown on substrate, where Akt stimulation occurs independently of Rac. We now show that V12Rac-mediated stimulation of Akt is not restricted to the hematopoietic lineage but is dependent on the adherence status of the cell. V12Rac-mediated stimulation of Akt as well as molecular association between Rac and Akt occurred exclusively in cells kept in suspension. Stimulation and complex formation are dependent on SHIP but in a manner that differs from its role in dephosphorylation of phosphoinositide lipids. Adherent cells lacking SHIP, but not those lacking PTEN, are able to activate Akt through the Rac pathway. Our data reveal the existence of a bona fide Rac to Akt signaling pathway, tightly regulated by SHIP and operational in suspended cells only. This pathway may point to an alternative survival signal that is called into action when cells lose contact with the substrate and/or with other cells.
|
巻・号 |
27(13)
|
ページ |
1876-85
|
公開日 |
2008-3-20
|
DOI |
10.1038/sj.onc.1210830
|
PII |
1210830
|
PMID |
17906692
|
MeSH |
Apoptosis
Blotting, Western
Cell Adhesion*
Cells, Cultured
Humans
Immunoprecipitation
Inositol Polyphosphate 5-Phosphatases
Mutation / genetics
PTEN Phosphohydrolase / metabolism
Phosphatidylinositols / metabolism
Phosphoric Monoester Hydrolases / metabolism*
Phosphorylation
Plasmids
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction*
rac GTP-Binding Proteins / metabolism*
|
IF |
7.971
|
引用数 |
8
|
WOS 分野
|
ONCOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
DT40(RCB1464) |